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ChemBio3D v.14 User Guide

1. Chapter 14 File Formats 227 of 318 ChemBio3D 14 0 Perkin For the Better 1 2651 1 6852 0 2712 5 P 2 1275 1 8656 1 4899 21 101 Figure 14 1 A Cart Coords 1 table for cyclohexanol 1 The first line of data contains the number of atoms in the model Optionally you can follow the number of atoms in the file with crystal cell parameters for the crystal structure a b c a B and y Following the cell parameters you can also include an exponent If you include an exponent then all of the fractional cell coordinates will be divided by 10 raised to the power of the exponent 2 The first line of a Cartesian coordinate file is followed by one line of data for each atom in the model Each line describing an atom begins with the symbol for the atom This symbol corresponds to a symbol in the Elements table The symbol can include a charge such as N The symbol is followed by the serial number 3 The serial number is followed by the three coordinates of the atom If you have specified crystal cell parameters in the first line of the file then these numbers are the fractional cell coordinates Otherwise the three numbers are X Y and Z Cartesian coordinates 4 Following the coordinates is the atom type number of the atom type for this atom This number corresponds to the code of an atom type record specified in the file format atom type table For more information see Editing file format atom types on page 224 5 Follow
2. I cos2 l cos3 Torstoms The V 2 parameter is the torsional force constant It determines the amplitude of the curve The n signifies its peri odicity no shifts the entire curve about the rotation angle axis The parameters are determined through curve fitting techniques Unique parameters for torsional rotation are assigned to each bonded quartet of atoms based on their atom types C C C C C O C N H C C H ChemBio3D provides three torsional parameters tables Torsional parameters a 4 Membered ring torsions a 3 Membered ring torsions Non bonded energy The non bonded energy represents the pair wise sum of the energies of all possible interacting non bonded atoms within a predetermined cut off distance The non bonded energy accounts for repulsive forces experienced between atoms at close distances and for the attractive forces felt at longer distances It also accounts for their rapid falloff as the interacting atoms move farther apart by a few Angstroms van der Waals energy Repulsive forces dominate when the distance between interacting atoms becomes less than the sum of their contact radii In ChemBio3D repulsion is modeled by an equation which combines an exponential repulsion with an attractive dispersion interaction 1 R6 n a 712SR 4 E van der Waals bey 290000e 2 25R where The parameters include n R and R the van der Waals radii for the atoms a Epsilon e determines
3. 6 Click OK To print 1 Go to File gt Print The Print dialog box opens 2 Click OK Chapter 3 Basic Model Building 31 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better Finding structures online ChemBio3D includes online resources from which you can download structures and view them in the model window For example you can download files from the Protein Data Bank PDB Crystallographic Information File CIF or Available Chemicals Exchange ACX databases To download a PDB or CIF file you will need either its PDB or CIF number To download an ACX file you will need either its ACX number or the structure name i Caution If the ChemDraw panel is open while you are downloading large structures you may receive an error message The number of atoms in this molecule exceeds the atom synchronization limit The ChemDraw panel cannot load the molecular structure Close the error message The downloaded structure will appear in the model window but not in the ChemDraw panel PDB and CIF files To download either a PDB or CIF file Goto Online gt Find Structure from PDB ID A dialog box opens Inthe dialog box either enter the PDB ID for the structure in the PDB ID drop down list or select it from the list Inthe Format drop down list select either PDB or CIF To enter a location to save the file select Save As to navigate to the save location an A OO N Click Get File The file is downloaded a
4. 6521 6583 3894 2458 0164 pP PerkinElmer For the Better 253 of 318 ChemBio3D 14 0 Perkin For the Better Each line is either a blank line a section header or a data record containing multiple fields of information about the com pound The SYBYL MOL2 file is broken down into several sections of information Record type indicators RTI break the information about the molecule into sections RTI s are always preceded by an sign Individual fields are delim ited by space s or a tab The fields in the SYBYL MOL2 format file used by Chem3D Proare as follows 1 Line 1 is a comment field The pound sign preceding the text indicates a comment line Name is a field designating the name of molecule The molecule name is the file name when the file is created using Chem3D Pro 2 Line 2 is a blank line 3 Line 3 lt TRIPOS gt MOLECULE is a Record Type Indicator RTI which begins a section containing inform ation about the molecule s contained in the file Note There are many additional RTIs in the SYBYL MOL2 format Chem3D Pro uses only lt TRIPOS gt MOLECULE lt TRIPOS gt ATOM and lt TRIPOS gt BOND 4 Line 4 contains the name of the molecule The name on line 4 is the same as the name on line 1 5 Line 5 contains 5 fields describing information about the molecule The first field is the number of atoms the second field is the number of bonds the third field is the number of
5. CONECT CONECT CONECT CONECT CONECT CONECT END The ATOM or HETATM record contains the record name followed by the serial number of the atom being described the element symbol for that atom then the X Y and Z Cartesian coordinates for that atom A CONECT record is used to describe the atomic connectivity The CONECT records contain the record name fol lowed by the serial number of the atom whose connectivity is being described then the serial numbers of the first atom second atom third atom and fourth atom to which the described atom is connected FORTRAN formats o a The full description of the COMPND record format in Protein Data Bank files is as follows Column Number Column Description Used by ChemBio3D Record Name COMPND Yes Chapter 14 File Formats 244 of 318 ChemBio3D 14 0 Perkin For the Better The description of the ATOM and HETATM record formats in Protein Data Bank files is Column Number Column Description Used by ChemBio3D 4 Record Name HETATM or ATOM We 1 1 UNUSED 13 16 Atom Name Element Symbol Alternate Location Indicator No 18 20 Residue Name Optional UNUSED 2 2 23 26 Residue Sequence Number 28 30 UNUSED 6 11 7 1 7 31 38 X Orthogonal A coordinates 39 46 ts Code for insertions of residues No ae Y Orthogonal A coordinates i Temperature Factor Footnote Number The full description of the CONECT record format in Protein Data B
6. Namide zo t aromatic N aromatic E Chapter 1 About ChemBio3D 2 of 318 ChemBio3D 14 0 Perkin For the Better Serial numbers and technical support The serial number is a unique key that helps you install and activate the ChemBioOffice application on your computer This is the same number you entered when you launched your ChemBioOffice application for the first time If you have lost your installation instructions you can find the serial number from the application Go to Help gt About ChemBio3D The serial number appears in the dialog box For more information on obtaining serial numbers and registration codes see the online Services Web site Technical support is available to registered users through the Internet and our Technical Support department When contacting Technical Support always provide the serial number and version number of your ChemBioOffice applic ation Our Technical Support Web pages contain answers to frequently asked questions FAQs and other inform ation To access our Technical Support in ChemBio3D go to Online gt Browse CambridgeSoft Technical Support If you are unable to find a solution on the Web site follow these steps before you contact Technical Support 1 Check the system requirements for the software 2 Read the Troubleshooting section and follow the possible resolution tactics outlined there 3 If all your attempts to resolve a problem fail contact technical support Try to repro
7. ROSDAL is a product of Softron Inc Chapter 14 File Formats 264 of 318 ChemBio3D 14 0 PerkinElmer For the Better References MEP The Molecular Electrostatic Potential MEP is the potential energy of a proton near a molecule The MEP is typically visualized by mapping the MEP values onto the surface reflecting the molecules boundaries This surface called elec tron density surface is obtained by plotting the points where the electron density of the molecule s wave function has a constant value Electron density is the measure of the probability of an electron being present at a specific location It is calculated using the formula P r SYP 16 790 7 ov Where p r electron density is a function of the coordinates r and is defined so that p r dr is the number of electrons in a small volume dr a 6 1 and r are basis functions Pis the density matrix The density matrix is a self adjoint positive semidefinite matrix of trace one that describes the statistical state of a quantum system Density matrix is given by the formula P Dl ERN j Where a pis the density operator which is interchangeably used with density matrix coefficients p are non negative and add up to one n y gt is state of the quantum system You can calculate molecular properties such as electron density or spin density for a regular grid of points in space and save it as a cube file A cube fi
8. q l E 69 120 gt cosa s J lij D D l where the value 69 120 converts the result to units of kcal mole Bond dipole parameters u for each atom pair are stored in the bond stretching parameter table The charge q is stored in the atom types table The molecular dielectric expression is set to a constant value between 1 0 and 5 0 in the MM2 Atom types table F Note ChemBio3D does not use a distance dependent dielectric Cutoff parameters The use of cutoff distances for electrostatic terms as for van der Waals terms greatly improves the computational speed for large molecules by eliminating long range interactions from the computation As in the van der Waals calculations ChemBio3D uses a fifth order polynomial switching function to maintain second order continuity in the force field The switching function is invoked as minimum values for charge charge charge dipole or dipole dipole interactions are reached These cutoff values are located in the MM2 Constants para meter table Since the charge charge interaction energy between two point charges separated by a distance r is proportional to 1 r the charge charge cutoff must be rather large typically 30 to 40 depending on the size of the molecule The charge dipole dipole dipole interactions fall off as 1 2 1 9 and can be cutoff at much shorter distances for example 25 and Chapter 9 Computation Concepts 177 of 318 ChemBio3D 14 0 Perkin For the Better
9. Changing bond order using command To change the bond order using a command 1 Right click a bond The bond will turn to yellow color 2 Point to Set Bond Order and choose a bond order Changing bond order by changing the type of an atom at one of the bond extremes This method is applicable only if you change a higher bond order to a lower bond order If you apply this method to change a lower bond order to a higher bond order a single bond is generated and valency is completed with hydro gens To change the bond order by changing an atom type on any end of the bond Chapter 3 Basic Model Building 13 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 1 Click the Build from Text tool 2 Click the atom that is attached to the bonds whose order you want to change 3 Enter the new atom type that will replace the selected atom In the following example we are replacing the Carbon C by an lodine I Untitied 1 gt x ChemDraw Livelink a x QO Q Oe Chem SMNES 4 Press ENTER The bond order of the bond changes to reflect the new atom type untitied 1 gt x ChemDraw Livelink a x QO Qy Oe Chemssmmes Changing several bonds at once To change several bonds at once 1 Open the ChemDraw panel and click in it to activate the ChemDraw control 2 Choose either the Lasso or Marquee tool 3 SHIFT click the bonds to change 4 Right click in the selected area and do one of the followi
10. a Copy Picture to copy the chart to the clipboard a Copy Data to copy the chart data to the clipboard a Save Picture to save the picture as an image file a Print to print the chart Tutorial 6 Overlaying Models Use overlays to compare the structural similarities between two models or conformations of the same model ChemBio3D provides two overlay techniques You can use either a fastoverlay algorithm or a manual method based on minimization calculations This tutorial describes the fast overlay method For the minimization method see Comparing models by overlay on page 61 The minimization method is more accurate but the fast overlay algorithm is more faster In both tutorial examples you superimpose a molecule of methamphetamine on a molecule of epinephrine Adrenalin to demon strate their structural similarities To overlay the two molecules you must first create them 1 Goto File gt New 2 Go to View gt Model Explorer if the model explorer is not already open Chapter 17 Tutorials 301 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 3 Choose the Build from Text tool Al from the Building toolbar and click in the model window A text box appears 4 Type Epinephrine use capital E and press ENTER A molecule of epinephrine appears _ Note When you capitalize the molecule s name ChemBio3D uses the substructures table to generate the struc ture and the structure name appears in the model exp
11. iS Cen I To calculate Mulliken populations using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Mulliken Charges 3 Click OK An alternative method 1 Go to Calculations gt GAMESS Interface gt Compute Properties 2 Inthe Properties tab select Mulliken Populations and click Run The results appear in the Output window and the Atom Property table m z The mass to charge ratio is a physical quantity used in the electrodynamics of charged particles Two particles with the same m z ratio move in the same path in a vacuum when subjected to the same electric and magnetic fields To report the mass to charge ratio 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select m z 3 Click OK Number of HBond Acceptors The number of hydrogen bond acceptors in the model To report the value 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Number of HBond Acceptors 3 Click OK Number of HBond Donors The number of hydrogen bond donors in the model To report the value Chapter 11 Chemical properties 208 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Number of HBond Donors 3 Click OK Num Rotatable Bonds The number of rotatable bonds in a molecule A rotatable bond is defined as an acyclic bond drawn as a single bond amide C N bon
12. AtOMmANd Dond SiZ nure e see cee bbe Deseo eee eects Mtoe eh demas 36 Displaying dot surfaces _ 2 222 222 00eeeeeee 36 Sen MUMDCIS 7 oath ee he eee Ate TEREN Yl Nie tn ete ton 37 Displaying atomS ce 38 Atomy mMDOIS naa ee sete Ng ga a eee e a iets aie E eet cla 39 Rotating models 22 2522 44 4 e bese a iaar e a cited de bees ea aR cece aea eee aa e aeia 40 Atom and bond properties 22 22 22222 eee ee cece ccc eee 000000000000 ceeeeeeceeeeeceeeteeeeeeeees 43 Showing hydrogen bonds 2 2 2 0 0 eee 44 Hydrogens and lone pairs _ 2 2 2 2 eee 45 Translating models 000 222 cece eee cece ccc ccc cece cece ee ee eee eee eee b eb beeeeeeeeeteeeeeeeeeeeeeeeeseeeeseeees 46 Scaling Modele fp ne oo atten os soe ee aire aris a ioe eat Ade eect a anne tn sla a Pa ata ween tide aie 46 Aligning models 0 00202 c cece cece ccc cece ccc cece ee cee cece eee e eee eeeebeeeeeeeeeeececeeeccssececeeceeeees 46 Applying COlOm 222 222 25 22522 foc E 25h thea dee te onc oat Seen odes a eh SU De Scenes i Sea ee 48 Model Explorer ce sos 522 26 east ua sect ec eo ht gees See te ee ane ee te a Beeson ee 51 Measuring molecules lt ccc e225 ede he ced eed KA ete de sade eee Lied eee EaR ESSE 58 Comparing models by overlay 2 22 2 eee 61 Molecular Surtaces prsest dy tae seca gute ss teeter Git pE dete ve vecel eee eyed bed eho 62 Using stereo pairs 02 cece cece cece cece cece cece cece cece eee eeeceeccecece
13. Chapter 3 Basic Model Building 28 of 318 hemBio3D 14 I SnemMPIO 9 PerkinElmer For the Better 3 Inthe other software application paste the model into an open file For example in Microsoft Word type lt Ctri gt lt V gt After you paste the model into the application you can edit it when needed To edit a pasted model 1 Inthe application in which the model is pasted double click the model image The model opens in ChemBio3D 2 In ChemBio3D edit the model 3 In ChemBio3D go to File gt Exit amp Return ChemBio3D closes Copying as a static image You can copy a model as either a bitmap or enhanced meta file EMF Bitmap files retain the background you see in ChemBio3D while the EMF adopts the background typically white used in the application in which it is pasted Figure 3 1 A model of asparagine imported as a bitmap left and as an EMF right When pasted into other applications these files become static images and cannot be modified However bitmap and EMF files typically have a smaller file size than embedded models To copy and paste a model as a static image 1 Select the model 2 Go to Edit gt Copy As and choose either Bitmap or Enhanced Metafile 3 Inthe other software application paste the model into an open file For example in Microsoft Word type CTRL V When you copy in a graphic format the size of the model window determines the size of the file that you copy to the clipboard from
14. Mol Refractivity Is a measure of the total polarizability of one mole of a substance It is dependent on the temperature index of refrac tion and pressure The molar refractivity A is expressed as _ 4a A 3 ae Where N N is the Avogadro constant and a is the mean polarizability To report the Mol Refractivity using either ChemPropPro or ChemPropStd 1 Go to Calculations gt Compute Properties 2 Expand either ChemPropPro or ChemPropStd and select Mol Refractivity 3 Click OK This is the sum of the atomic weights of all atoms in a molecule To report the mass 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Mol Weight 3 Click OK Molecular Mass The mass of one molecule of a substance measured in atomic units au To calculate molecular mass using Gaussian 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select Molecular Mass 3 Click OK Chapter 11 Chemical properties 205 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Molecular Surfaces To calculate molecular surfaces using GAMESS 1 Go to Calculations gt GAMESS Interface gt Compute Properties 2 Inthe Properties tab select Molecular Surfaces and click Run To calculate molecular surfaces using Gaussian 1 Go to Calculations gt Gaussian Interface gt Compute Properties 2 Inthe Properties tab select Molecular Surfaces and click Run Molecular Topological Index
15. SF 9 Angles f Note The default value of the sextic force constant is 0 00000007 To precisely reproduce the energies obtained with Allinger s force field set the sextic bending constant to O in the MM2 Constants tables There are three parameter tables for the angle bending parameters Angle Bending parameters a 3 Membered Ring Angle Bending parameters 4 Membered Ring Angle Bending parameters There are three additional angle bending force constants available in the MM2 Constants table These are the CHR Bending constants specifically for carbons with one or two attached hydrogens The CHR Bending Ko for 1 1 1 angles allows more accurate force constants to be specified for Type 1 CHR and Type 2 CHR interactions The CHR Bending Ko for 1 1 1 angles in 4 membered rings and the CHR Bending Ky for 22 22 22 angles in 3 membered rings require separate constants for accurate specification Torsion energy Erwin X f cos nd Torsioss lt The numbers in the angle definitions refer to the Text column in the Atom Types Table 1 refers to C alkane and 22 refers to C cyclopropane Chapter 9 Computation Concepts 174 of 318 hemBio3D 14 I ChemBio3 0 PerkinElme For the Better This term accounts for the tendency for dihedral angles torsionals to have an energy minimum occurring at specific intervals of 360 n In ChemBio3D n can equal 1 2 or 3 AJ Fa V 1 cos
16. 0 477 0 0 139 1 324 0 1 396 0 445 0 2 1708 1 2238 0 1 0068 0 343 1 0 284 1 7936 1 0 147 1 9741 0 2 375 1 032 0 1 589 sald els 1 2546 202 1 2 0091 161 0 0 077 893 1 Chapter 14 File Formats 250 of 318 ChemBio3D 14 0 PerkinE For the Better 0 21 2 076 0 0419H 2 308 1 08 0 8816H 1 372 0 2442 1 6545H 2 9386 0 6891 0 8100H The following illustration shows the components of the SYBYL Output File from ChemBio3D for C 6 and Bond 3 of Cyclohexanol The format for SYBYL MOL files is as follows 1 The first record in the SYBYL MOL File contains the number of atoms in the model the word MOL the name of the molecule and the center of the molecule 2 The atom records lines 2 20 in the cyclohexanol example contain the Atom ID in column 1 followed by the Atom Type in column 2 and the X Y and Z Cartesian coordinates of that atom in columns 3 5 Chapter 14 File Formats 251 of 318 ChemBio3D 14 0 Perkin For the Better 3 The first record after the last atom records contains the number of bonds in the molecule followed by the word MOL 4 The bond records lines 22 40 in the cyclohexanol example contain the Bond Number in column 1 followed by the Atom ID of the atom where the bond starts the From Atom in column 2 and the Atom ID of the atom where the bond stops the To Atom in column 3 The last column in the b
17. 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Water Solubility 3 Click OK Chapter 11 Chemical properties 215 of 318 ChemBio3D 14 0 pP PerkinElmer For the Better Wiener Index Provides measure of branching defined as ai 7 poe Where D are the off diagonal elements of the distance matrix To calculate the Wiener Index 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Wiener Index 3 Click OK Zero Point Energy 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select Zero Point Energy 3 Click OK ChemBioFinder properties The properties listed below can be calculated in ChemBioFinder Ultra for ChemBioOffice 2014 For more information on these properties and how to calculate them see the ChemBioFinder online help B Balaban Index Boiling Point Cc Chemical Name Cluster Count Critical Pressure Critical Temperature Critical Volume Connolly Accessible Area Connolly Molecular Area Connolly Solvent Excluded Volume E Elemental Analysis Exact Mass F Chapter 11 Chemical properties H Heat of Formation Henry s Law Constant I Ideal Gas Thermal Capacity L LogP LogS M Mass Melting Point Mol Formula Mol Formula HTML Mol Refractivity Mol Weight Molecular Topological Index P Partition Coefficient pKa Polar Surface Area Principal Moment R Radius S Sha
18. 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select Heat Capacity 3 Click OK Heat of Formation Reported in KJ mole the heat of formation is the increase in enthalpy resulting from the formation of one mole of a sub stance from its constituent elements at constant pressure To report the heat of formation 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Heat of Formation 3 Click OK Henry s Law Constant A unitless value Henry s Law Constant can be expressed as kH pc Chapter 11 Chemical properties 198 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Where p is the partial pressure of the solute in the gas above the solution c is the concentration of the solute and ky ae is aconstant with the dimensions of pressure divided by concentration The constant known as the Henry s law constant depends on the solute solvent and temperature To report the heat of formation 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Henry s Law Constant 3 Click OK Hyper Polarizability To calculate hyper polarizability using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Hyper Polarizability 3 Click OK Hyperfine Coupling Constants To calculate hyperfine coupling constants using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface
19. 1 2 2 1 torsional parameter of 2 butene The values of V1 and V2 in the Torsional Parameters table are 0 100 and 10 000 respectively Because a positive value of V2 indicates that there are minima at 0 and 180 these minima signify cis 2 butene and trans 2 butene respectively Notice that V2 for torsional parameters involving torsions about carbon carbon double bonds all have values ranging from approximately V2 8 000 to V2 16 250 In addition V2 torsional parameters Chapter 7 Parameter Tables 151 of 318 ChemBio3D 14 0 Perkin For the Better involving torsions about carbon carbon single bonds all have values ranging from approximately V2 2 000 to V2 0 950 The values of V2 for torsions about carbon carbon double bonds are higher than those values for torsions about car bon carbon single bonds A consequence of this difference in V2 values is that the energy barrier for rotations about double bonds is much higher than the barrier for rotations about single bonds The V1 torsional constant creates a torsional energy difference between the conformations represented by the two tor sional energy minima of the V2 constant As discussed previously a negative value of V1 means that a torsional energy minimum occurs at 0 and a torsional energy maximum occurs at 180 The value of V1 0 100 means that cis 2 butene is a torsional energy minimum that is 0 100 kcal mole lower in energy than the torsional energy maximum represented by trans 2 but
20. 14 0 PerkinElmer For the Better 3 Press ENTER A model of ethane appears f Note When automatic rectification is on the free valence in the ethyl group is filled with a hydrogen If automatic rec tification is off you need to type EtH to get the same result For substructures with more than one atom with an open valence explicitly specify terminal atoms for each open valence Example 2 Building with a substructure and other elements To build a model with substructures and other elements 1 Using the Build from Text tool click in the model window 2 Type PrNH2 into a text box with no atoms selected 3 Press ENTER A model of propylamine appears Example 3 Polypeptides To use substructures for building biopolymers such as proteins 1 Type HAlaGlyPheOH into a text box with no atoms selected The additional H and OH cap the ends of the poly peptide If you don t cap the ends and automatic rectification is on ChemBio3D tries to fill the open valence f Note For amino acids that repeat avoid re typing the amino acid by putting parenthesis around the repeating unit fol lowed by the number of times it repeats For example type HAla Pro 10GIlyOH 2 Press ENTER f Note If the substructure contains two or more open valences ChemBio3D 14 0 creates a bond between the open valence sites to create a ring The alpha form of the neutral polypeptide chain composed of Alanine Glycine and Phenylalanine appears F Not
21. 16 160 is 1 0078 1 0078 15 9994 18 0106 The exact mass of heavy water containing two hydrogen 2 deuterium or 2H and one oxygen 16 160 is 2 014 2 014 15 9994 20 027 To determine the exact mass 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Exact Mass 3 Click OK Formal Charge The formal charge is the charge assigned to an atom in a molecule assuming that electrons in a chemical bond are shared equally between atoms regardless of relative electronegativity The formal charge of an atom in a molecule can be calculated using the formula FC V N B 2 Where V is the number of valence electrons of the atom in isolation atom in ground state N is the number of non bonding electrons on this atom in the molecule and B is the total number of electrons shared in covalent bonds with other atoms in the molecule To report the formal charge Chapter 11 Chemical properties 196 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Formal Charge 3 Click OK Frequencies To calculate infrared vibrational frequencies using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Frequencies 3 Click OK To calculate frequencies using Gaussian 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select Frequencies 3 Cli
22. 2 tool 2 Click drag anywhere in the model window The Status bar displays the X and Y axes of rotation Rotating a fragment You can also rotate one or more fragments that you select To rotate one or more fragments 1 Select an atom in each fragment you want to rotate 2 Select the rotation tool hold the SHIFT key and click drag anywhere in the model window Axis rotations You can rotate your model around the X Y and Z axes These axes are defined by the model window The hori zontal and vertical axes of the window define the X and Y axes of rotation the Z axis is perpendicular to the window These axes are independent of the view and model axes For more on the view and model axes see Object position on page 23 Chapter 4 Displaying Models 40 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 E 3 z e 3 ED Rotate About Y Axis Figure 4 3 The rotation bars A Bond rotation bar X X axis rotation bar Y Y axis rotation bar Z Z axis rotation bar To rotate a model around either the X Y or Z axis 1 optional Go to View gt Model Display gt Model Axes to display the view axes 2 Select the Rotate tool 3 Point to an edge of the model window the rotation bars appear 4 Click drag the pointer around the rotation bar for the axis you want to rotate the model around The angle of rotation appears in the Status bar Hiding rotation bars By default the
23. 318 ChemBio3D 14 0 Perkin For the Better 1 A matrix called the Fock matrix is initialized to represent the favorability of sharing electrons between pairs of atoms in api system 2 The pi molecular orbitals are computed from the Fock matrix 3 The pi molecular orbitals are used to compute a new Fock matrix then this new Fock matrix is used to compute better pi molecular orbitals 4 Step 2 and step 3 are repeated until the computation of Fock matrix and the pi molecular orbitals converge This method is called the self consistent field technique or a pi SCF calculation 5 A pi bond order is computed from the pi molecular orbitals 6 The pi bond order is used to modify the bond length BL_ and force constant KS for each sigma bond in the pi system 7 The values of KS and BL are used in the molecular mechanics portion of the MM2 computation to further refine the molecule To examine the computed bond orders after an MM2 computation 1 Inthe Pop up Information control panel select Bond Order 2 Position the pointer over a bond The information box contains the newly computed bond orders for any bonds that are in a pi system CS MOPAC This section provides additional information about the MOPAC that has not be covered in other areas of the ChemBio3D documentation a Potential energy functions a Adding parameters to MOPAC a Electronic configuration includes using MOPAC sparkles ChemBio3D supports MO
24. 7 2 4 8 9 5 3 7 h2 5H 1H3 A model can consist of multiple structures Each structure is defined as a fragment 7 Note Water is considered a solvent Each water molecule you add to your model constitutes one fragment Using the Name to Structure N2S tool To build a model from text 1 Select the Build from Text tool on the Building toolbar 2 Click in the model window A text field appears 3 Inthe text field either type or paste the name of the structure and press ENTER Tip Here are several tips to keep in mind while using the text tool to build models 1 Text is case sensitive For example to specify an oxygen atom type O 2 You can add a formal charge using text For example type PhO to create a model of a phenoxide ion instead of Y phenol 3 When you double click an atom the content of the previous text box are applied to that atom If several atoms are selected The contents of the text box are applied to each atoms independently 4 Not all text substitutions make sense For example selecting two atoms in the same chain with a label of ben zene will not work The interpretation of the text in a text box depends on whether atoms are selected as follows f nothing in the model window is selected a new molecule is added f one or more atoms selected the text is added to the selection unless the specifications for the selected atom are violated When a text box is visible you can modify
25. AutoDock where to explore the docking space To define a cavity you select atoms or groups at points of your choosing along the cavity boundary ChemBio3D calculates the centroid of the cavity using your selec tion s and defines a grid box around the centroid You adjust position and size number of grid points and spacing between points of the grid box to enclose the selected atoms or groups along the cavity boundary that you want AutoDock to use in the calculation The AutoDock calculation is confined to the defined grid box If any named groups have been defined in Step 3 make sure that these groups are excluded inside the grid box otherwise the ligand will have no chance to interact Chapter 8 Docking 159 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Before computing the docking AutoDock builds a series of grid maps one per ligand atom type Each grid map is con structed by placing a probe atom of an atom type at each grid point and computing its interaction energy with the receptor During docking a ligand is posed inside the grid box and its interaction energy with the protein is computed using the grid maps Figure 8 1 A protein with the grid box inside a cavity the box is shown here in white for clarity Figure 8 2 An illustration of the grid box in two dimensions with a ligand pose and calculated energy grid points To prepare the cavity 1 Inthe AutoDock Interface select the Prepare GPF tab 2 In
26. Better C 104 C 12 21 2863 5 0000 C 108 C 16 21 1957 5 0000 C 22 C 114 20 6472 5 0000 C 34 C 126 20 1410 20 3860 C 45 C 137 20 3218 C 50 C 142 20 4350 The distances in the Actual cell may differ because they depend on how the second polymer was positioned relative C 28 C 120 20 7001 5 0000 C 133 C 41 to the first polymer when the second polymer was created To begin the alignment computation 1 Go to Structure gt Align The Align dialog box appears 2 Type 0 100 for the Minimum RMS Error value and 0 010 for the Minimum RMS Gradient Dock 2x Minimum RMS Error 0100 Minimum AMS Gradient o o 0 IV Display Each Iteration J Record Each Iteration Cancel The docking computation stops when the RMS Error or the RMS Gradient becomes less than the Minimum RMS Error and Minimum RMS Gradient value 3 Click Display Each Iteration This lets you see how much the fragments have moved after each iteration of the docking computation 4 Click Start Note that while the alignment computation proceeds one molecule remains stationary and the second molecule moves Chapter 17 Tutorials 305 of 318 ChemBio3D 14 0 PerkinElmer For the Better To stop the alignment computation before it reaches its preset RMS values click Stop Calculation on the Cal culation toolbar Alignment and recording are stopped The status bar displays the values describing each iteration The illustratio
27. Chapter 3 Basic Model Building 12 of 318 ChemBio3D 14 0 Perkin For the Better Using bond tools Use the bond tools to create the basic structure of your models Subsequently you can modify it to look the way you want For example you can change the carbons or hydrogens to other elements or hide the hydrogens to reduce clut ter on the screen a S A Figure 3 1 The Building toolbar includes the single double triple and dummy bond tools To create a model using bond tools Choose a bond tool such as the Single Bond tool Inthe Model window click and drag in the direction you want the bond to be oriented Release the mouse button to complete the bond To add more bonds click and drag from an atom you just drew aR wD 3 Tochange an atom click it with the Build from Text tool tA selected and enter the new atom symbol For example to change a hydrogen atom to a chlorine atom a Click the hydrogen atom A text box appears b Type Cl in the text box c Press ENTER Changing bond order To change the bond order of one or more bonds at a time you can use the bond tools commands or the Build from Text tool You can also change the bond order for bonds attached to an atom by changing the atom type See Build ing types on page 140 Changing bond order with a bond tool To change the bond order with a bond tool 1 Select a bond tool of a different order 2 Click drag from one atom to another atom
28. Click the Select tool A Select C 1 Chapter 17 Tutorials 294 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better 3 Go to Structure gt Invert The cis isomer appears You can rotate the model to see the differences between the isomers after you invert the molecule Using Substructures Labels are useful for building simple structures However to make larger more complex structures you may find it easier to use a combination of labels and predefined substructures Over 200 substructures are predefined in ChemBio3D These include the most commonly used organic structures Tip Predefined substructures are listed in the substructures xml file To view the list go to View gt Parameter Tables gt Substructures Text you type in the text box is case sensitive you must type it exactly as it appears in the Substructures table To build a model of nitrobenzene using substructures 1 Go to File gt New 2 Click Build from Text tool 3 Click the empty space in the Model window 4 Type Ph NOZ2 in the text box 5 Press ENTER A model of nitrobenzene appears The substructure in this example is the phenyl group as indicated by Ph Substructures are defined with specific attachment points for other substituents For phenyl the attachment point is C 1 To build a peptide model 1 Go to File gt New 2 Click Build from Text tool 3 Click an empty space in the Model window A text box appea
29. Close Window Nano d Saving to Dropbox ChemBio3D files may be saved to Dropbox as a repository for files to be shared with others or the ChemBio3D iPad app To use Dropbox services you must have a A valid Dropbox account and a ChemBio3D installed Chapter 2 ChemBio3D Basics 10 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better You can upload your drawings from the current ChemBio3D document windows to your remote Dropbox folder loc ation You can later download these files when required Upload files You can upload your drawing in the current document window in ChemBio3D to your remote Dropbox folder To upload a file Go to File gt Save As Specify the name of the file Select the file format in which you want to upload the drawing Change the current folder setting to Desktop gt Yourname systemfolder gt Dropbox gt Select a folder location to save the file ono FR O N Optional If you want to change the file name enter the new file name in the File name textbox at the bottom of the dialog box f Note If you have used the ChemBio3D iPad app to save to Dropbox the ChemBio3D folder will already exist in Dropbox If you haven t you will need to create the folder on your own 7 Click Save Download files You can download the files from your remote Dropbox folder to your local machine When download is complete the drawing automatically appears in the ChemBio3D document window
30. Defining groups 0 00000 eee cece e cece eee oaao aaae aaran aranna 159 Step 4 Preparing the cavity prepare GPF 222222 c cece ccc ccc cece ccc cece cece ccc e cece cece ete eeeteeees 159 Step 5 Selecting pose parameters Prepare DPF 0 0 2 cee cece cece eee eeeeeceeeeeeeees 161 cS oo DIO0 41a 0 cn 162 Step 7 Viewing Docking Results 0000 000 e cece cece cece eeeececeeseeeeeeeees 163 FRETENENCCS moar an eat oe Sot oe Pete ele here ns A a Seat ena aaa 163 Chapter 9 Computation Concepts 2 2 22 e cece e cece eeeeceeeecceeeees 164 Computational chemistry overview cece cece eee cece cece cece eaaa oaoaraa raaraa nanana 164 Computational methods overview 22 222 22c cc ccce cece cece cece cece cece ccc ceeeeeeeeeeeeceteceeeeeeeeeees 164 Uses of computational methods 2 2 2 2 22 cece eee cece eee cece cece cece cece cece eee eceeececeeeteeeeeees 165 Geometry optimization 2 2 22 e cece cece ccc eee ce ceeccceeececceeeeeeeeeeees 165 Choosing the best method 2 2 cece eee e cece cece cece cece cece cece cece cee eeececeeeeeeeeeeeees 167 Molecular mechanics theory in brief 0 00 000000 e cece cece eeeeeeeeeeceeeeeeeees 171 Thetorcetield she xc 2 se ee ee hk tts a I A Ap ee EEES 171 Molecular dynamics simulation 00 0 000000 c ccc ce eee e cece cece eeeeeeeeeeeeeceeeeesseees 179 Chapter 10 ChemScript 2 0
31. Formaldehyde model 5 Go to Calculations gt MOPAC Interface gt Minimize Energy 6 On the Theory tab choose AM1 7 On the Properties tab select Dipole 8 Click Run The results shown in the Messages window indicate the electron distribution is skewed in the direction of the oxygen atom Dipole vector Debye 2 317 0 000 0 000 2 317 Chapter 6 Computational Engines 121 of 318 ChemBio3D 14 0 PerkinElmer For the Better If you rotate your model the X Y and Z components of the dipole differ However the total dipole does not In this example the model is oriented so that the significant component of the dipole lies along the X axis Example 2 Cation stability This example compares cation stabilities in a homologous series of molecules To build the model Go to File gt New Click the Build from Text tool Click in the model window A text box appears For tri chloro type C CI3 and press ENTER Repeat step 1 through step 4 for the other cations type C Cl2 for di chloro type C Cl for mono chloro and CH3 for methyl cation ao A O N f Note The cations in this example are even electron closed shell systems and are assumed to have Singlet ground state No modifications through additional keywords are necessary The default RHF computation is used To perform the computation 1 Go to Calculations gt MOPAC Interface gt Minimize Energy 2 On the Theory tab choose AM1 3 On the Properti
32. MM2 Angle Bending parameters table is for an alkane carbon with two non hydrogen groups attached Angle bending parameters for car bons with one or two attached hydrogens differ from those for carbons with no attached hydrogens Because carbons with one or two attached hydrogens frequently occur separate force constants are used for these bond angles Chapter 7 Parameter Tables 148 of 318 ChemBio3D 14 0 PerkinElmer For the Better The CHR Bending K for 1 1 1 angles allows more accurate force constants to be specified for the Type 1 CH2 and Type 2 CHR interactions In addition the CHR Bending K for 1 1 1 angles in 4 membered rings and the CHR Bending K for 22 22 22 angles 22 is the atom type number for the C Cyclopropane atom type in 3 membered rings differ from the aforementioned CHR Bending K for 1 1 1 angles and thus require separate constants to be accurately specified Stretch Bend Parameters a X B C N O Y Stretch Bend interaction force constant a X B C N O H Stretch Bend interaction force constant a X AI S Y Stretch Bend force constant a X AI S H Stretch Bend force constant a X Si P Y Stretch Bend force constant a X Si P H Stretch Bend force constant a X Ga Ge As Se Y Stretch Bend force constant The stretch bend parameters are force constants for the stretch bend interaction terms in the prior list of elements X and Y represent any non hydrogen atom When an angle is compressed the MM2 force field uses th
33. Networks and select pKa 3 Click OK Polar Surface Area The Polar Surface Area PSA is defined as the surface sum over all polar atoms usually oxygen and nitrogen includ ing attached hydrogens To calculate the PSA 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Polar Surface Area 3 Click OK Polarizability The polarizability is defined as the ratio of the induced dipole moment of an atom to the electric field E that pro duces this dipole moment The formula to calculate polarizability is Tel E To calculate polarizability using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Polarizability 3 Click OK An alternative method 1 Go to Calculations gt GAMESS Interface gt Compute Properties 2 Inthe Properties tab select Polarizability and click Run To calculate polarizability using Gaussian 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select polarizability 3 Click OK An alternative method 1 Go to Calculations gt Gaussian Interface gt Compute Properties 2 Inthe Properties tab select polarizability and click Run The results appear in the Output window Chapter 11 Chemical properties 210 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Potential Energy Is an energy stored within a system In a molecular system potential energy is present in the chemical bonds ina
34. Objects tool W in the Building toolbar 2 Select one or more objects to select multiple objects SHIFT click each one 3 Click drag one of the selected objects When you move an atom attached rectification atoms typically hydrogens move with it When you move a bond its adjacent atoms also move You can also use the Translate tool w to move objects 1 Select one or more objects in the model window 2 While pressing SHIFT click drag the selected object s using the translate tool Centering a selection When resizing a model or before performing computations it is often useful to center the model ChemBio3D lets you select an atom or atoms to determine the center or perform the calculation on the entire model To center your model based on a selection 1 Optional Select one or more atoms Chapter 3 Basic Model Building 23 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better 2 Go to Structure gt Model Position gt Center Model or Selection on Origin This command places the centroid of the selected atoms at the origin of the model axes ChemBio3D calculates the centroid of the selected atoms by averaging their X Y and Z coordinates If you do not select any atoms the whole model becomes centered Substructures A substructure is simply part of a structure basically a building block that you can define and use to quickly build models Substructures have attachment points to which other atoms or substr
35. Rotation dial Chapter 6 Computational Engines 114 of 318 ChemBio3D 14 0 PerkinElmer For the Better Figure 6 5 The Rotation dial 6 Hold down the S key and select the bond between the C 1 and C 2 atoms _ Note Holding down the S key temporarily activates the Select tool 7 Select one of the dihedral rotators then enter 57 in the text box and press ENTER A nearly eclipsed conformation of ethane is displayed Tip To view this better rotate the model on the Y axis until the carbon atoms are aligned Use CS MOPAC to create the precise eclipsed transition state 1 Holding down the S and SHIFT keys click any two nearly eclipsed hydrogen atoms such as H 4 and H 7 to identify the dihedral to track You should have a nearly coplanar four atom chain such as H 4 C 1 C 2 H 7 selected 2 Go to Structure gt Measurements gt Generate All Dihedral Angles The Measurement table appears and displays an actual value for the selected dihedral angle of about 3 degrees this will vary slightly between experiments 3 Go to Calculations gt MOPAC Interface gt Optimize to Transition State 4 Click Copy Measurements to Messages in the Job Type tab 5 Click Run The ethane model minimizes so that the dihedral is 0 degrees corresponding to the eclipsed con formation of ethane a known transition state between the staggered minima conformations To see the Newman projection of the eclipsed ethane model 1 Select bot
36. The Open dialog box appears 2 Select the file to run The dialog box corresponding to the type of job Minimize Energy Compute Properties and so on saved within the file appears 3 Click Run Repeating a Gaussian job After you perform a Gaussian calculation you can repeat the job as follows 1 From the Gaussian submenu choose Repeat name of computation A dialog box appears 2 Change parameters if desired and click Run The computation proceeds CONFLEX CONFLEX is a conformational analysis package developed by the CONFLEX Corporation Using CONFLEX you can search for low energy conformers of a model and create a fragment for each one in its optimal state ChemBio3D is currently using Conflex version 6 8 9 To use CONFLEX ensure that your model consists of only one fragment Each low energy conformer that CONFLEX finds appears as a separate fragment in the model explorer Energy minimization CONFLEX interface also helps you perform energy minimization of molecules It supports the following force fields a MM2 a MM3 a EMM2 a MMFF a MMFF94S To perform energy minimization 1 Build a model of the structure 2 Go to Calculations gt CONFLEX Interface gt Minimize Energy Geometry The CONFLEX Interface dialog box appears 3 Inthe Job amp Theory tab select from these options a Select the Energy Potential Chapter 6 Computational Engines 109 of 318 pP Perkin For the Better ChemBio3D 14 0
37. These display modes are global options but you can override their effect by changing the display mode of a particular atom or group in the model explorer Hydrogens and lone pairs To show all hydrogen atoms or lone electron pairs in the model go to View gt Model Display and select either a Show hydrogen atoms gt Show All Show Lone Pairs gt Show All Chapter 4 Displaying Models 45 of 318 ChemBio3D 14 0 PerkinE For the Better Translating models You can pan your view of the model vertically and horizontally using the translate tool No objects in the window move you just change the position from which you view the model the effect is similar to using scroll bars ina Web browser To translate a model 1 Select the Translate tool Na on the Building toolbar 2 Click drag anywhere in the model window You can also use the translate tool to move objects 1 Select one or more objects in the model window 2 While pressing SHIFT click drag the selected object s using the translate tool Scaling models With the zoom tool E selected click and drag vertically in the model window to magnify or reduce the model size The coordinates of the model do not change You can also use the wheel if you are using a scrolling mouse You can scale a model to fit the window that contains it To scale a model to the window go to View gt View Position gt Fit to Window 7 Note The Fit command affects only the scale of the model Atomic
38. You can save the file in a desired location To download a file 1 Go to File gt Open 2 Change the current folder setting to Desktop gt Yourname systemfolder gt Dropbox gt 3 Do one of the following a Double click the file that you want to download a Browse to a file that you want to download and click Open _ Note You can specify a time limit for the download process to complete by specifying a value in seconds in the Time out limit textbox You can specify any value between a minimum of 5 seconds and a maximum of 120 seconds as the time out limit Chapter 2 ChemBio3D Basics 11 of 318 ChemBio3D 14 0 PerkinE ag For the Better Basic Model Building A model can consist of one or more molecular structures solvents ions or just one atom There are several basic ways to build a model Build the model one bond at a time using the model building tools See Using bond tools on page 13 a Draw a2D structure in the ChemDraw panel and convert the structure to a 3D model See The ChemDraw panel on page 6 Enter the name of the chemical structure into the model window using the Build from Text tool See Building from text on page 16 Enter a chemical name or SMILES in the ChemDraw panel Youcan also build models by importing model data from a table See Building with Cartesian tables on page 86 Usually a combination of these methods yields the best results For example you might build a carbon skel
39. a number of factors including a The nature and size of the molecule a The type of information sought a The availability of applicable experimentally determined parameters as required by some methods Computer resources The three most important criteria are a Model size The size of a model can be a limiting factor for a particular method The limiting number of atoms ina molecule increases by approximately one order of magnitude between method classes from ab initio to molecular mechanics Ab initio is limited to tens of atoms semiempirical to hundreds and molecular mechanics to thou sands a Parameter Availability Some methods depend on experimentally determined parameters to perform com putations If the model contains atoms for which the parameters of a particular method have not been derived that method may produce invalid predictions Molecular mechanics for example relies on parameters to define a force field A force field is only applicable to the limited class of molecules for which it is parametrized Computer resources Requirements increase relative to the size of the model for each of the methods Ab initio The time required for performing computations increases on the order of N4 where N is the number of atoms in the model Semiempirical The time required for computation increases as N or N2 where N is the number of atoms in the model MM2 The time required for performing computations increases as N2 where N
40. and select Hyperfine Coupling Constants 3 Click OK ideal Gas Thermal Capacity The thermal capacity at constant volume of an ideal gas is f Cy ae cyNk cynR Where Cy is a constant dependent on temperature U is the internal energy T is the absolute temperature V is the volume n is the amount of substance of the gas R is the gas constant 8 314 JKT Imor inSI units N is the number of gas particles k is the Boltzmann constant 1 381 x10723JKT T in SI units Chapter 11 Chemical properties 199 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 The thermal capacity at constant pressure of an ideal gas is 2 Cp 37 y 1 Nk Where H is the enthalpy of the gas calculated as H U pV To report the ideal gas thermal capacity 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Ideal Gas Thermal Capacity 3 Click OK Internal Energy The internal energy is the total energy due to the motion of molecules plus the rotation and vibration of atoms within molecules It can be calculated using dU TdS PdV udN Where a dU is the change in internal energy a Tis the temperature a dS is the change in Entropy a pis the pressure a dV is the change in volume a wis the chemical potential a dN is the number of particles added to the system To calculate internal energy using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand G
41. another development environment you can either edit the scripts provided with ChemBioOffice or cre ate your own Regardless of how you develop a script it must include these commands Chapter 10 ChemScript 183 of 318 ChemBio3D 14 0 Perkin For the Better from sys import from os import from os path import from ChemScriptl4 import The first command imports the python system The second and third commands import the operating system mod ules The last command imports all the ChemScript functions After you include these command lines how you develop the rest of your script is entirely up to you Introducing the ChemScript API ChemScript includes a ChemScript API reference guide You can find the guide at Start gt All Programs gt ChemBioOffice 2014 gt ChemScript 14 0 gt API Reference It provides links and information for the ChemScript classes The ChemScript object model comprises two fundamental levels of functionality described below ChemScript Classes At the top level the API consists of four classes Atom Chemical element charge bonds to neighboring atoms drawing coordinates 3D coordinates if available ste reochemistry etc Bond Bonded atoms bond order etc Molecule Mol A chemical connection table which can represent one or more molecular fragments This class also includes file I O capabilities and other advanced chemistry functionality such as stereochemistry Reaction Rxn A chemical
42. atom name and the X Y and Z coordinates for each atom The order of atoms is determined by their serial numbers All the atoms in a fragment are listed in consecutive records Hydrogen lone pair and dummy atoms are listed last As in other tables you can edit values in the table and the model will update to reflect the change To display the Cartesian coordinates table go to View gt Cartesian Table Comparing models by overlay Use the overlay feature to lay one molecule on top of another This is useful for when you want to compare structural similarities between models with different compositions or compare conformations of the same model For example assume you want to compare structural similarities between methamphetamine and epinephrine Go to File gt New to open a new model window Select the Build from Text tool and click in the model window A text box appears Type Epinephrine and press ENTER A molecule of Epinephrine appears Click in the model window below the Epinephrine molecule A text box appears oa A OO N Type Methamphetamine and press ENTER A molecule of methamphetamine appears beneath the epinephrine molecule After building the two structures you must identify at least three pairs of atoms that will be used to apply the overlay Each pair composes of one atom that you select from each structure F Note Atom Pair consists of two atoms that are a specified distance apart and are in different fra
43. b Select an Optimization Method c Select the Max Computation Time 4 Inthe General tab select from these options a Select a directory in the Results in field The directory is where the calculation results file will be stored b Optional Select a directory in the Backup Calculations Files A backup file is stored in the location you select c Select Output files to display in notepad The files you select will appear in text files after the calculation is com plete a INI This file reports the options you selected in the Job amp Theory tab a BSO This file reports structural and thermodynamic properties of the model 5 Click Run 6 Click Yes in the confirmation box that appears if you want to bring back the minimized molecule in to ChemBio3D 7 Note If you have opted for the output files to display in notepad in the General tab you can view the INI file and BSOfile as soon as the job is completed Conformation search To search for conformers 1 Build a model of the structure 2 Go to Calculations gt CONFLEX Interface gt C onformation Search The CONFLEX Interface dialog box appears 3 Inthe Job amp Theory tab select from these options a Select the Energy Potential b Select an Optimization Method c Select the Max Computation Time d Select the Conformation Search Limit 4 Inthe General tab select from these options a Select a directory in the Results in field The directory is where the cal
44. between the benzene rings Figure 17 34 A biphenyl model with the C C bond selected To calculate the rotational bond energy 1 Using the selection tool click the C C bond between the rings 2 Go to Calculations gt Dihedral Driver gt Single Angle Plot The calculation begins During the calculation the model window displays the model being rotated around the selected bond while the Output window reports the energy value at each incremental angle Examining the lowest highest energies When the calculation is complete the Dihedral Driver Chart opens displaying a graph of the energy in kcal versus the angle of rotation around the C C bond the same data appears in the Output window To view the conformation at any given point 1 Inthe chart click any location along the curve The model display rotates the dihedral to the selected con formation 2 Tosee the conformation energy through a range of rotation angles click and drag across the chart while viewing the model Chapter 17 Tutorials 316 of 318 ChemBio3D 14 0 I PerkinElmer For the Better Dihedral Driver Chart x Conformational Energy Energy kcal mol 10 0 180 135 90 45 0 45 90 135 180 C 2 Cf1 C 7 C 8 degrees Figure 17 35 Single angle plot of the diphenyl C C bond with minimization turned on The dihedral rotates in 5 degree increments through 360 degrees for a total of 72 conformations to produce the graph You can view the minimized ene
45. box appears 3 Choose a color and click OK To revert to the default color 1 Select the group or groups 2 Right click your selection 3 On the context menu go to choose Color gt Apply Group Color and select Inherit Group Color Resetting defaults To remove changes use the Reset Children to Default command on the context menu Chapter 4 Displaying Models 55 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Group labels When you create a group it is listed using a generic name in the model explorer You can change the name and dis play it in the model window To set group labels 1 Go to View gt Model Explorer if the model explorer isn t open already 2 Inthe model explorer right click one of the groups in the list 3 Inthe context menu select Group Labels and choose the desired option Figure 4 8 group labels Displaying group labels You can display group labels in your model To display labels right click a group name in the model explorer click Group Labels in the context menu and select an option Inherit Settings the label appears if the parent group appears Show Group Label this group and children display the group and child groups Show Group Label this group only display only this group Does not affect child groups a Hide Group label this group and children Hide this group and its child groups Moving objects You group objects together move objects in and out o
46. charge using the Build from Text tool or by specifying it in MOPAC To add the charge to the model 1 Click the Build from Text tool 2 Click an atom in your model 3 Type a charge symbol For example click a carbon and type in a text box to make it a carbocation The charge is automatically sent to MOPAC when you do a calculation To specify the charge in MOPAC 1 Go to Calculations gt MOPAC Interface and choose a calculation The MOPAC Interface dialog box appears Chapter 15 References 272 of 318 ChemBio3D 14 0 Perkin For the Better 2 On the General tab in the Keywords box type the keyword CHARGE n where n is a positive or negative integer 2 1 1 2 Different combinations of spin up alpha electrons and spin down beta electrons lead to various electronic energies These combinations are specified as the Spin Multiplicity of the molecule The following table shows the relation between total spin S spin multiplicity and the number of unpaired electrons Ce al snc lowes To determine the appropriate spin multiplicity consider whether The molecule has an even or an odd number of electrons a The molecule is in its ground state or an excited state Touse RHF or UHF methods The following table shows some common permutations of these three factors RHF Closed Shell Chapter 15 References 273 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 eom fore T T poje mer
47. contains only lines describing the Z matrix for the atoms in that frame f Note For data file specifications see the online MOPAC manual To edit a file to run using the Run MOPAC Input File command 1 Open the MOPAC output file in a text editor The output file below shows only the first four atom record lines The first line and column of the example output file shown below are for purposes of description only and are not part of the output file Col 1 Col 2 C3 Col 4 C5 Col 6 Col 7 Col 8 Line 1 Line 2 Cyclohexanol 0 0 1 54152 1 MacroModel is produced within the Department of Chemistry at Columbia University New York N Y Chapter 14 File Formats 262 of 318 For the Better 1 53523 1 111 77 1 0 0 1 53973 1 109 7 1 55 69 1 2 InLine 1 type the keywords for the computations you want MOPAC to perform blank in the example above Line 2 is where enter the name that you want to assign to the window for the resulting model However ChemBio3D ignores this line 3 Leave Line 3 blank 4 Line 4 through Ln were nis the last atom record include the internal coordinates optimization flags and con nectivity information for the model Column 1 is the atom specification Column 2 is the bond distance for the connectivity specified in Column 8 a Column 3is the optimization flag for the bond distance specified in Column 2 a Column 4 is the bond angle for the connectivity specified in Column 8 a Column 5
48. dialog box the nature of the serialization of your model determines whether a consistent Z matrix can be constructed If the serial numbers in the Z matrix which is about to be created are not consecutive a message appears You are wamed if the atoms in the model must be reserialized to create a consistent Z matrix When you select the Int Coords format you have several options To specify the save options 1 Click Save As 2 Select the Int Coords format in the Save As dialog box 3 Select from these options Use Current Z matrix Save your model using the Z matrix described in the Internal Coordinates table of the model Only Serial Numbers Bond and Dihedral Angles Build a Z matrix in which the current serial number ordering of the atoms in the model is preserved in the Z matrix Pro R Pro S and Dihedral angles are used to position atoms Only Serial Numbers Dihedral Angles Only Build a Z matrix in which the current serial number ordering of the atoms in the model is preserved in the Z matrix The Pro R and Pro S stereochemical designations are not used in constructing the Z matrix from a model All atoms are positioned by dihedral angles only Chapter 14 File Formats 261 of 318 ChemBio3D 14 0 Perkin For the Better MacroModel files The MacroModel MCM DAT OUT file formats are defined in the MacroModel Structure Files version 2 0 doc umentation ChemBio3D supports import of all three file types and can export MCM Maes
49. display arrows that indicate the direction of the vibration a Displacement control the range of movement of atoms a Speed control the speed of the animation 5 Click play 6 To stop the animation click stop 7 Toreturn the model to its original starting position click reset NMR spectra You can use GAMESS to predict the 13 and 1H NMR spectra of your model After ChemBio3D calculates the spec trum the spectrum appears in the spectrum viewer where you can view print or save it NMR spectra are saved in cdx file format and can be opened in ChemBioDraw To view any spectrum that has been calculated select it at the top of the spectrum viewer To create an NMR spectrum 1 Go to Calculations gt GAMESS Interface gt Predict NMR Spectrum Chapter 6 Computational Engines 136 of 318 ChemBio3D 14 0 Perkin For the Better 2 Inthe GAMESS Interface dialog box select the desired options and click Run To either save or print the spectrum right click in spectrum and select either Save as or Print Saving customized job descriptions After you customize a job description you can save it as a Job Description file to use later For more information see Job description file formats on page 108 To save aCS GAMESS job 1 On the General tab type the file name in the Menu Item Name text box The name you choose will appear in the GAMESS menu 2 Click Save As The Save dialog box appears 3 Open the folder Chem3D C3D Ex
50. ee avn fae o fee me cafn e po ef e ef e e fe fe e eh Ee po e e sf o e o ee e is fe aDo not use OPEN n1 n2 for ground state systems except for high symmetry systems with open shells Chapter 15 References 274 of 318 ChemBio3D 14 0 PerkinElmer For the Better Electronic State Spin State fone O o ooo oe sewer Even electron systems If a molecule has an even number of electrons the ground state and excited state configurations can be Singlet Triplet or Quintet not likely Normally the ground state is Singlet but for some molecules symmetry considerations indicate a Triplet is the most stable ground state Ground State RHF The Ground State RHF configuration is as follows Singlet ground state the most common configuration for a neutral even electron stable organic compound No addi tional Keywords are necessary Triplet ground state Use the following keyword combination TRIPLET OPEN 2 2 Quintet ground state Use the following keyword combination QUINTET OPEN 4 4 f Note The OPEN keyword is normally necessary only when the molecule has a high degree of symmetry such as molecular oxygen The OPEN keyword increases the active space available to the SCF calculation by including virtual orbitals This is necessary for attaining the higher multiplicity configurations for even shell system The OPEN keyword also invokes the RHF computation using the 1 2 electron approxim
51. high resolution values can also take a long time to calculate The default setting of 30 is a good compromise between speed and smoothness To set the resolution 1 Go to Surfaces gt Resolution The Resolution slider appears 2 Adjust the slider to the desired resolution Chapter 4 Displaying Models 64 of 318 ChemBio3D 14 0 PerkinElmer For the Better The new resolution is the middle value listed at the bottom of the Resolution tool Surface colors Setting the molecular surface color depends on the type of surface For setting color in Solvent Accessible Connolly Molecular or Total Charge Density surfaces go to Surfaces gt Color Mapping gt Surface Color and select the new color For Total Spin Density Molecular Electrostatic Potential and Molecular Orbital surface types you must specify two colors On the Surfaces menu choose Color A or Color B Surface mapping The Mapping property provides color coded representations of atom colors groups of atoms hydrophobicity partial charges and electrostatic potential superimposed on the solvent accessible surface Surface Color Is the color you have chosen for the molecular surface Atom Color Is based on the displayed atom colors these may or may not be the default element colors Element Color Is based on the default colors in the Elements Table Group Color Is based on the colors if any you specified in the model explorer when creating groups Hydrophobicity Is displa
52. improvements they have been found to be limited in certain situations The two major questions to consider when choosing a potential function are Is the method parameterized for the elements in the model a Does the approximation have limitations which render it inappropriate for the model being studied For more detailed information see the MOPAC online manual MNDO applicability and limitations MNDO may be applied to the shaded elements in the table below E 3 ie al Ga Gelas Se Er Kr 7 The following limitations apply to MNDO a Sterically crowded molecules such as neopentane are too unstable a Four membered rings such as in cubane are too stable a Hydrogen bonds are virtually non existent for example water dimer Overly repulsive nonbonding interactions between hydrogens and other atoms are predicted In particular simple hydrogen bonds are generally not predicted to exist using MNDO a Hypervalent compounds such as sulfuric acid are too unstable a Activation barriers are generally too high a Non classical structures are predicted to be unstable relative to the classical structure for example ethyl radical a Oxygenated substituents on aromatic rings are out of plane for example nitrobenzene a The peroxide bond is systematically too short by about 0 17 A a e The C O C angle in ethers is too large AM1 applicability and limitations AM1 may be applied to the shaded elements in the table b
53. in the model window and even overlay the structures This is useful for tasks such as examining drug like molecules and their inter actions within a receptor By default the Structure Browser is collapsed and appears as a vertical tab left of the model window Hover the mouse over the tab to display the Structure Browser Chapter 2 ChemBio3D Basics 7 of 318 ChemBio3D 14 0 PerkinE For the Better To import structures into the structure browser 1 Go to File gt New to open a new document window 2 Go to File gt Import File to import a file that contains the structures to view _ Note You can import structural data from either an SD file sybyl mol2 file sm2 file or an ml2 file After you import the file the structures from the file are listed as fragments in the model explorer To browse the struc tures you must first drag the structures from the model explorer into the structure browser 1 Click the auto hide icon in the model explorer and in the structure browser windows so that both windows remain open 2 Click and drag a fragment from the model explorer window into the structure browser window The structure names are copied to the structure browser 3 Drag more fragments as desired from the model explorer to the structure browser To view or hide each structure in the structure browser select or de select its corresponding check box a acheck in the box indicates the structure is in view a an empty box indic
54. is as follows 15 1X ATOMS 1X 15 1X BONDS number of atoms number of bonds atom serial number type 16 A4 3 F9 4 and coordinates bond id from atom to atom bond type 16 15 16 2X A8 Chapter 14 File Formats 226 of 318 ChemBio3D 14 0 PerkinElmer For the Better Cartesian coordinate files ChemBio3D lets you save models in Cart Coords 1 or Cart Coords 2 file formats These file formats store the atom types coordinates and attached atoms for each atom in a model These file formats also interpret fractional cell coordinates in orthogonal or non orthogonal coordinate systems The difference between the two file formats are the codes used to convert atom type numbers in the file into atom types that ChemBio3D uses In Cart Coords 1 atom types are numbered according to the numbering used by N L Allinger in MM2 These numbers are also generally followed by the program PC Model In Cart Coords 2 the atom type number for all atom types is computed by multiplying the atomic number of the element by 10 and adding the num ber of valences as specified by the geometry of the atom type These numbers are also generally followed by the pro gram MacroModel For example the atom type number for C Alkane a tetrahedral carbon atom is 64 using Cart Coords 2 To examine the atom types described by a file format see Editing file format atom types on page 224 The format for a Cartesian coordinate file is
55. is the number of atoms In general molecular mechanical methods are computationally less expensive than quantum mechanical methods The suitability of each general method for particular applications can be summarized as follows Molecular mechanics methods Molecular mechanics in ChemBio3D 14 0 apply to a Systems containing thousands of atoms a Organic oligonucleotides peptides and saccharides Chapter 9 Computation Concepts 167 of 318 ChemBio3D 14 0 PerkinE For the Better Gas phase only for MM2 Useful techniques available using MM2 methods include a Energy Minimization for locating stable conformations a Single point energy calculations for comparing conformations of the same molecule Searching conformational space by varying one or two dihedral angles Studying molecular motion using Molecular Dynamics Quantum mechanical methods Useful information determined by quantum mechanical methods includes Molecular orbital energies and coefficients Heat of Formation for evaluating conformational energies Partial atomic charges calculated from the molecular orbital coefficients Electrostatic potential Dipole moment Transition state geometries and energies Bond dissociation energies Semiempirical methods available in ChemBio3D 14 0 with Gaussian apply to Systems containing up to 120 heavy atoms and 300 total atoms a Organic organometallics and small oligomers peptide nucleo
56. keywords sent to CS MOPAC and those you can use to affect this property UHF Sent to CS MOPAC if you choose Open Shell Unrestricted wave functions to specify the use of the Unrestricted Hartree Fock meth ods GEO OK Sent to CS MOPAC to override checking of the Z matrix MMOK Sent to CS MOPAC to specify Molecular Mechanics correction for amide bonds Use the additional keyword NOMM to turn this keyword off SPIN You can add this keyword to print the spin density matrix in the out file Chapter 6 Computational Engines 120 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 RHF spin density RHF Spin Density uses the 1 2 electron correction and a single configuration interaction calculation to isolate the alpha spin density in a molecule This method is useful when the UHF Spin Density computation becomes too resource intensive for large molecules For more information see the MOPAC online manual This table contains the keywords sent to CS MOPAC and those you can use to affect this property Sent to CS MOPAC to specify RHF spin density calculation GEO OK Sent to CS MOPAC to override checking of the Z matrix Example 1 Dipole moment This example describes how to calculate the dipole moment for formaldehyde 1 Go to File gt New Model 2 Click the Build from Text tool 3 Click in the model window A text box appears 4 Type H2CO and press ENTER A model of formaldehyde appears amp Figure 6 6
57. methyl groups of 2 butene The two alkene carbons are the central atoms of the dihedral angle vi The V1 or 360 Periodicity Torsional constant field contains the first of three principal torsional constants used to compute the total torsional energy in a molecule V1 derives its name from the fact that a torsional constant of 360 periodicity can have only one torsional energy minimum and one torsional energy maximum within a 360 period The period starts at 180 and ends at 180 A positive value of V1 means that a maximum occurs at 0 and a minimum occurs at 180 in a 360 period A neg ative value of V1 means that a minimum occurs at 0 and a maximum occurs at 180 in a 360 period The sig nificance of V1 is explained in the example following the V2 discussion V2 The V2 or 180 Periodicity Torsional constant field contains the second of three principal torsional constants used to compute the total torsional energy in a molecule V2 derives its name from the fact that a torsional constant of 180 periodicity can have only two torsional energy minima and two torsional energy maxima within a 360 period A positive value of V2 indicates there are minima at 0 and 180 and there are maxima at 90 and 90 in a 360 period A negative value of V2 causes the position of the maxima and minima to be switched as in the case of V1 above A good example of the significance of the V1 and V2 torsional constants exists in the
58. molecule and also in forces between molecules To calculate potential energy using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Potential Energy 3 Click OK An alternative method 1 Go to Calculations gt GAMESS Interface gt C ompute Properties 2 Inthe Properties tab select Potential Energy and click Run The results appear in the Output window 3 Click Run The results appear in the Output window Principal Moment This refers to the principal moments of inertia about the principal axes of a molecule The moments of inertia are com puted for a series of straight lines through the center of mass using the formula I Snad i Where l is the moment of inertia mjs are point masses whose distances from the rotation axis are denoted by d s Distances are established along each line proportional to the reciprocal of the square root of on either side of the center of mass The locus of these distances forms an ellipsoidal surface The principal moments are associated with the principal axes of the ellipsoid If all three moments are equal the molecule is considered to be a symmetrical top If no moments are equal the molecule is considered to be an unsymmetrical top To report the principal moment 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Principal Moment 3 Click OK The eccentricity of an atom is the largest value in its
59. of the lsocontour tool Solvent radius You can set the solvent radius using the slider The default solvent radius is 1 4 A the value for water Radii for other common solvents are shown below Chapter 4 Displaying Models 65 of 318 ChemBio3D 14 0 PerkinElmer For the Better Methanol 1 9 Ethanol Acetonitrile Acetone Pyridine 2 4 Chloroform 2 7 To set the solvent radius 1 Go to Surfaces gt Solvent Radius The Radius slider appears 2 Adjust the slider to the desired resolution The new radius is the middle value listed at the bottom of the Radius tool Extended Huckel Extended H ckel is a basic semi empirical method that you can use to generate molecular surfaces rapidly for most molecular models Applying an Extended HUckel calculation is a common preliminary step for predicting surfaces using more sophisticated methods To compute molecular surfaces using the Extended Huckel method go to Calculations gt Extended Huckel gt Cal culate Surfaces _ Note Before performing an Extended Hiickel calculation ChemBio3D deletes all lone pairs and dummy atoms At this point a calculation has been performed and the results of the calculation are stored with the model To compute partial charges using the Extended H ckel method go to Calculations gt Extended Hiickel gt Calculate Charges For each atom in the model a message is created listing the atom and its partial charge If you have selected Partial Char
60. on the starting geometry the potential energy function used and the settings for a minimum acceptable gradient between steps convergence criteria Chapter 9 Computation Concepts 165 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better The following illustration shows some concepts of minimization For simplicity this plot shows a single independent variable plotted in two dimensions Potential Energy Variable The starting geometry of the model determines which minimum is reached For example starting at b minimization results in geometry a which is the global minimum Starting at d leads to geometry f which is a local min imum The proximity to a minimum but not a particular minimum can be controlled by specifying a minimum gradient that should be reached Geometry f rather than geometry e can be reached by decreasing the value of the gradient where the calculation ends In theory if a convergence criterion energy gradient is too lax a first derivative minimization can result ina geometry that is near a saddle point This occurs because the value of the energy gradient near a saddle point as near a min imum is very small For example at point c the derivative of the energy is 0 and as far as the minimizer is con cerned point c is a minimum First derivative minimizers cannot as a rule cross saddle points to reach another minimum _ Note If the saddle point is the extremum of inte
61. over all gen erations A sort of safety valve to stop the calculation running forever The number must be a positive integer The default value is 250000 Docking Number of automated docking runs Typical values that are often used range from 5 to 15 Docking cal culation time increases as this value increases Chapter 8 Docking 161 of 318 ChemBio3D 14 0 Perkin For the Better To enter the pose parameters 1 Inthe AutoDock Interface select the Prepare DPF tab 2 Enter the pose parameters in the Parameter fields AutoDock saves the values in the dpf file displayed in the Advanced Options field 3 Optional To edit the DPF file manually click Edit under Advanced Options The DPF file opens in a text editor and you can make necessary changes Caution It is not advisable to edit the DPF file manually Any mistake in the manual editing may block AutoDock from performing the docking job correctly 4 Click Run 5 Foran in depth explanation on these values see the AutoDock Web site Step 6 Docking By the time you are ready to start the docking calculation AutoDock has stored in log files all needed information about the ligand receptor and the binding sites You can edit this information in the log files before you run the cal culation AutoDock uses two files namely Grid Parameter File GPF and Docking Parameter File DPF to record information about the ligand receptor and the binding sites GPF specifies t
62. radii and interatomic distances do not change Fit Model to Window You can specify whether to resize and center the model in the model window whenever you make a change 1 Go to File gt Model Settings 2 Inthe Model Building tab select Fit Model to Window and click OK Aligning models You can align a model either to an axis or to a plane Aligning to an axis You can select any two atoms in a model and align them to either the X Y or Z axis The atoms don t have to be in the same structure 1 To view the axes select the Model Axes E and View Axes buttons in the model display toolbar 2 Select any two atoms 3 Goto Structure gt Model Position gt Align Model with X Y or Z Axis The model becomes oriented so that the two atoms you select are parallel to the chosen axis The command Align View X Y or Z Axis with Selection align the axis joining the selected atoms parallel to the X Y or Z axis where the Z axis is orthogonal to the screen the X axis runs from left to right and the Y axis runs down to up on the screen Chapter 4 Displaying Models 46 of 318 ChemBio3D 14 0 PerkinE For the Better To orient the selected atoms with the screen 4 Make sure the aligned atoms are still selected or reselect them 5 Go to View gt View Position gt Align View X Y or Z Axis with Selection For example to see an end on view of ethanol 1 Click the Select tool 2 SHIFT click C 1 and C 2 X _ wx
63. row or column of the distance matrix and represents how far away from the molecular center it resides Chapter 11 Chemical properties 211 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 The diameter D is the maximum such value for all atoms and is held by the most outlying atom s Examples Dia meter of methane 0 ethane 1 propane 2 n butane 3 The radius R is the minimum such value and is held by the most central atom s Examples Radius of methane 0 ethane 1 propane 1 n butane 2 To calculate the radius 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Radius 3 Click OK The root mean square force 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select RMS Force 3 Click OK An alternative method 1 Go to Calculations gt Gaussian Interface gt Compute Properties 2 Inthe Properties tab select RMS Force and click Run SCF Energy The self consistent field method for determining the ground state wave function of a quantum many body system To calculate the SCF energy Go to Calculations gt Compute Properties Expand Gaussian Interface and select SCF Energy Click OK Oo N An alternative method 1 Go to Calculations gt Gaussian Interface gt Compute Properties N Inthe Properties tab select SCF Energy and click Run Shape Attribute The shape attribute kappa measures the branc
64. select the Rectify check box Possible rectification types are a HAmine H Ammonium a H Carboxyl a H Enol a H Guanidine a H Thiol When you specify a rectification type the bound to type of the rectification type should not conflict with the building type If there is no rectification type for an atom it is never rectified For example if the rectification type of O Carboxyl is H Carboxyl the bound to type of H Carboxyl should be either O Carboxyl or empty Otherwise when assigning building types hydrogen atoms bound to O Carboxyl atoms are not assigned H Carboxyl Geometry The geometry for a building type describes the number of bonds that extend from this type of atom and the angles formed by those bonds These are the possible geometries Chapter 7 Parameter Tables 141 of 318 ChemBio3D 14 0 PerkinElmer For the Better a QLigand 1Ligand a Linear Octahedral Square planar Tetrahedral a Trigonal bipyramidal a Trigonal planar _ Note Standard bond angle parameters are used only when the central atom has a tetrahedral trigonal or bent geo metry Double Triple and Delocalized Bonds The number of double triple and delocalized bonds are integers ranging from zero to the number of ligands that the geometry specifies ChemBio3D uses this information both to assign building types based on the bond orders and to assign bond orders based on building types Bound to Order This is the acceptable order of t
65. should use the method described to follow this example Before minimizing use the Clean Up Structure command to refine the model This generally improves the ability of the Minimize Energy command to reach a minimum point 1 Goto Edit gt Select All 2 Goto Structure gt Clean Up To perform the minimization go to Calculations gt MM2 gt Minimize Energy and click Run When the minimization is complete reorient the model so it appears as in the figure below The conformation you converged to is not the well known chair conformation which is the global minimum Instead the model has converged on a local minimum the twisted boat conformation This is the closest low energy con formation to your starting conformation Had you built this structure using substructures that are already energy minimized or in the ChemDraw panel you would be close to the chair conformation The minimizer does not surmount the saddle point to locate the global min imum and the closest minimum is sought Note All parameters used are finalized Iteration 33 Minimization terminat Stretch 0 4328 Bend 0 7378 Stretch Bend 0 1285 Torsion 5 6010 Non 1 4 VDU 0 8813 1 4 VDU 5 8993 Total 11 9181 lt gt Chapter 6 Computational Engines 99 of 318 ChemBio3D 14 0 Perkin For the Better Figure 6 1 Energy values for twisted boat conformation The major contributions are from the 1 4 van der Waals and torsional aspects of the model For cyc
66. spring s bending angular force constant while 95 defines the equilibrium angle This equation estimates the energy Chapter 9 Computation Concepts 173 of 318 ChemBio3D 14 0 PerkinElmer For the Better associated with deformation about the equilibrium bond angle The constant 0 02191418 is a conversion factor to obtain the final units as kcal mole Unique parameters for angle bending are assigned to each bonded triplet of atoms based on their atom types C C C C O C C C H For each triplet of atoms the equilibrium angle differs depending on what other atoms the central atom is bonded to For each angle there are three possibilities XR2 XRH or XH2 For example the XH2 parameter would be used for a C C C angle in propane because the other atoms the central atom is bonded to are both hydro gens For isobutane the XRH parameter would be used for 2 2 dimethylpropane the XR2 parameter would be used The effect of the Kh and 0 A parameters is to broaden or steepen the slope of the parabola The larger the value of Ko the more energy is required to deform an angle from its equilibrium value Shallow potentials are achieved with Ko val ues less than 1 0 A sextic term is added to increase the energy of angles with large deformations from their ideal value The sextic bend ing constant SF is defined in the MM2 Constants table With the addition of the sextic term the equation for angle bending becomes E pma 0 02191418 K 8 9 f
67. substructures the fourth field is the number of features and the fifth field is the number of sets 7 Note Chem3D Pro ignores the following fields number of substructures number of features and number of sets These fields will contain zeros if the file was created using Chem3D Pro 6 Line 6 describes the molecule type This field contains SMALL if the file is created using Chem3D Pro 7 Line 7 describes the charge type associated with the molecule This field contains NO_CHARGES if the file is cre ated using Chem3D Pro 8 Line 8 blank in the above example might contain internal SYBYL status bits associated with the molecule 9 Line 9 blank in the above example might contain comments associated with the molecule _ Note Four asterisks appear in line 8 when there are no status bits associated with the molecule but there is a com ment in Line 9 10 Line 10 lt TRIPOS gt ATOM is a Record Type Indicator RTI which begins a section containing information about each of the atoms associated with the molecule Chapter 14 File Formats 254 of 318 ChemBio3D 14 0 PerkinElmer For the Better 11 Lines 11 29 each contain 6 fields describing information about an atom the first field is the atom id the second field is the atom name the third field is the X coordinate the fourth field is the Y coordinate the fifth field is the Z coordinate and the sixth field is the atom type Note Atom types are user definable See E
68. the depth of the attractive potential energy well and how easy it is to push atoms together n rj which is the actual distance between the atoms At short distances the above equation favors repulsive over dispersive interactions To compensate for this at short distances R 3 311 this term is replaced with Chapter 9 Computation Concepts 175 of 318 ChemBio3D 14 0 PerkinE For the Better E ander Walk 336 l 76 ZR The R and Epsilon parameters are stored in the MM2 Atom Types table For certain interactions values in the VDW interactions parameter table are used instead of those in the MM2 atom types table These situations include interactions where one of the atoms is very electronegative relative to the other such as in the case of a water molecule Cutoff parameters for van der Waals interactions The use of cutoff distances for van der Waals terms greatly improves the computational speed for large molecules by eliminating long range relatively insignificant interactions from the computation ChemBio3D uses a fifth order polynomial switching function so that the resulting force field maintains second order continuity The cutoff is implemented gradually beginning at 90 of the specified cutoff distance This distance is set in the MM2 Constants table The van der Waals interactions fall off as 1 18 and can be cut off at much shorter distances for example 10A This cut off speeds the computations significantly even for rela
69. the force constant for a non conjugated double bond taken from the Bond Stretching table The higher the value of K for the bond between two pi atoms the more difficult it is to compress or stretch that bond d Length The dLength field contains a constant used to increase the bond length of any conjugated double bond The bond length for a bond with a calculated pi bond order x is li I 1 x dLength where l is the bond length of a non conjugated double bond taken from the Bond Stretching table The higher the value of li for the bond between two pi atoms the longer that bond is The quality of a parameter indicates the relative accuracy of the data Accuracy Level The parameter is an estimate by ChemBio3D See Estim ated parameters on page 139 The parameter is derived from experimental data The parameter is well confirmed The reference for a measurement corresponds to a reference number in the References table References indicate The parameter is theorized but not confirmed where the parameter data was derived See the References parameter table for a list of references Chapter 7 Parameter Tables 146 of 318 ChemBio3D 14 0 Perkin For the Better Pi Atoms The Pi Atoms table Conjugated Pisystem Atoms xml contains the electron property parameters used to correct atoms in pi systems In ChemBio3D additional information is used to compute the pi system portions of the MM2 force field for the pi atoms Th
70. the model that are occupying the valence shells of that atom at any given instant By subtracting this average from the number of protons in the molecule the partial charge of each atom is determined Chapter 17 Tutorials 310 of 318 ChemBio3D 14 0 Perkin For the Better Visualizing the partial charge of the atoms in a molecule is another way to understand the model s reactivity Typically the greater the partial charge on an atom the more likely it is to form bonds with other atoms whose partial charge is the opposite sign Note ChemBio3D recognizes formal charges you assign to atoms in the model window and ChemDraw panel It then calculates delocalized charges for all atoms in the model where delocalization occurs To display formal and delocalized charges hover the mouse over a charged atom Using the theories in Extended Huckel CS MOPAC or Gaussian you can compute the partial charges for each atom In the following example the partial charges for phenol are computed by Extended HUckel 1 Go to the File gt New 2 Using the Text Building tool click in the model window 3 Type PhOH in the text box and press ENTER A molecule of phenol is created 4 To compute Extended Htckel charges go to Calculations gt Extended Huckel gt Calculate Charges The Atom Property table opens displaying the results To view the table at any time go to View gt Atom Property Table Displaying Partial Charges You can use gradient colors to
71. the name of an element atom type or substructure such as H20 for water 3 Press ENTER The fragment appears 4 Optional Double click a different location to add another fragment 7 Note Water is considered a solvent Each water molecule you add to your model constitutes one fragment Figure 3 2 Three fragments of an H2O model Selecting atoms and bonds Typically you must select atoms and bonds before you modify or move them To select an atom or bond in the display window 1 Click the Select tool 1Ionic compounds can consist of multiple fragments one for each ion Chapter 3 Basic Model Building 18 of 318 ChemBio3D 14 0 PerkinElmer For the Better 2 Click the atom or bond _ Note To select a bond you can either click the bond or select both of its adjacent atoms To select more than one atom hold down either the SHIFT or CTRL key while selecting the atoms To select all atoms and bonds in a model go to Edit gt Select All or type CTRL A The model explorer provides an alternate way of selecting atoms and bonds See Model Explorer on page 51 Selecting ungrouped atoms To select several atoms and bonds click and drag across them with either the Move Objects tool or Select tool LS Atoms that are least partially within the selection rectangle are selected when you release the mouse button A bond is selected only if both adjacent atoms are also selected Tip To select atoms one at a time o
72. the parameter data was derived See the References parameter table for a list of references van der Waals interactions The parameters contained in the van der Waals parameters table van der Waals Interaction xml are used to adjust specific van der Waals interactions ina molecule such as hydrogen bonding to provide better correspondence with Chapter 7 Parameter Tables 153 of 318 ChemBio3D 14 0 PerkinE For the Better experimental data in calculating the MM2 force field For example consider the van der Waals interaction between an alkane carbon Atom Type 1 and a hydrogen Atom Type 5 Normally the van der Waals energy is based on the sum of the van der Waals radii for these atoms found for each atom in the Atom Types table 1 900A for Atom type number 1 1 400A for Atom type number 2 3 400A However better correspondence between the computed van der Waals energy and experimental data is found by sub stituting this sum with the value found in the van der Waals Interactions table for this specific atom type pair Atom Types 1 5 3 340A Similarly an Eps parameter is substituted for the geometric mean of the Eps parameters for a pair of atoms if their atom types appear in the van der Waals Interactions table Chapter 7 Parameter Tables 154 of 318 ChemBio3D 14 0 PerkinE For the Better Docking Docking helps you determine how a small molecule a ligand may be arranged to fit inside a cavity in a larger molecule a rece
73. the substructures parameter table go to View gt Parameter Tables gt Substructures 2 Inthe substructure table select either the cell or the entire row that contains the substructure name 3 Right click the selected cell or row and select Copy from the context menu 4 Inthe model window type CTRL V or right click the window and select Paste from the context menu You can also use the text tool 1 Using the Build from Text tool click in the model window 2 Inthe text box type the name of the substructure and press ENTER The substructure appears in the model win dow _ Note The substructure table need not be open to use the text tool Adding a substructure to a model To attach a substructure to an existing model 1 Inthe model select the atom where you want to attach the substructure _ Note The atom you select will be replaced with the substructure 2 Right click the selected atom and select Replace with Text Tool 3 Inthe text box enter the name of the substructure and press ENTER Tip Go to View gt Parameter Tables gt Substructures for a list of substructure names Examples for using substructures Several examples for using substructures appear below Example 1 Building ethane To build a model of ethane using a substructure 1 Using the Build from Text tool click in the model window 2 Type Et or EtH into a text box with no atoms selected Chapter 5 Building Advanced Models 74 of 318 ChemBio3D
74. to the site of negative charge You can calculate the Dipole using either GAMESS or Gaussian To calculate the dipole using GAMESS 1 Go to Calculations gt GAMESS Interface gt C ompute Properties 2 Inthe Properties tab select Dipole and click Run 3 Optional To view the dipole in the model select Yes when prompted To calculate the dipole using Gaussian iN Go to Calculations gt Gaussian Interface gt Compute Properties Inthe Gaussian interface dialog box select the Jobs tab and then select the Properties tab Inthe Properties tab select the Dipole checkbox Click Run Optional To view the dipole in the model select Yes when prompted N O O Chapter 11 Chemical properties 193 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Electron Density Is the probability of an electron being present at a specific location It is calculated using the formula pr YY Ppt Where a p r electron density is a function of the coordinates r and is defined so that p r dr is the number of electrons in a small volume dr z 0 and r are basis functions a Pis the density matrix You can calculate the electron density using either GAMESS or Gaussian To calculate electron density using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Electron Density 3 Click OK An alternative method 1 Go to Calculations gt GAMESS Interface gt Compute Prop
75. types of adjacent atoms To rectify selected atoms in your model 1 Select the atoms to rectify 2 Go to Structure gt Rectify To set rectification as a default 1 Go to File gt Model Settings and select the Model Building tab 2 Select Rectify 3 Click OK F Note The rectification setting does not affect fragments that already appear in the model window To rectify exist ing atoms select the atoms and go to Structure gt Rectify When Correct Building Type and Rectify settings are selected in the Model Building tab panel the atom type is set according to the bond tool used and the appropriate number of hydrogens are added Rectifying atoms in PDB files While opening a PDB file you can specify that the hydrogens in the PDB file model be rectified To add hydrogens to PDB file 1 Go to File gt Open Chapter 3 Basic Model Building 27 of 318 ChemBio3D 14 0 Perkin For the Better 2 Select a PDB file to open 3 Select the following check boxes Compute Atom Types and Bond Orders a Rectify Atoms 4 Click Open Upon import hydrogens will be added to the molecule from the PDB file Cleaning up a model As you build your model or arbitrarily move objects around the model window your model may begin to appear dis torted To correct the distortion use the Clean Up command To clean up the selected atoms in a model 1 Select a part or all of the model to clean up 2 Go to Structure gt Clean Up When y
76. with respect to the scaffold See Example 006 script py 7 Note The overlay functionality can also be used to align three dimensional structures Example 7 Reaction Transformation This example demonstrates reaction transformation This means that you can draw a reaction that defines a trans formation of a molecule and then apply that transformation to a set of structure files All the files necessary for this tutorial are in the Example 007 directory The transform1 cdxm1 file provides the reaction that defines the transformation The input sdf file contains all the structures that will be transformed O R re ie Ye Figure 10 2 The transform file defines how the transformation is applied to the source structures The script searches the input file for structures that contain a nitro group shown as a reactant in the transformation file If a structure is found the script transforms the nitro group to the form shown in the product and copies the entire structure to a new file The figure below shows one example A B N Pi _ N 0 N 0 d Chapter 10 ChemScript 187 of 318 ChemBio3D 14 0 PerkinE For the Better Figure 10 3 A before the transformation is applied B after transformation Structures that don t meet the search criteria are ignored Example 8 Simple salt stripping The program reads an SD File identifies and removes salt components if any are present and outputs two SD files The
77. you back up the parameter files in the C3D Table directory For example to add a new parameter to the Torsional parameters table 1 Go to View gt Parameter Tables gt Torsional Parameters 2 Enter the appropriate data in each field of the parameter table Be sure that the name for the parameter is not duplic ated elsewhere in the table 3 Close and save the table Showing used parameters You can display in the Output window all parameters used in an MM2 calculation To show the used parameters go to Calculations gt MM2 gt Show Used Parameters The list includes a quality assessment of each parameter The empir ically derived highest quality parameters are rated as 4 while the best guess lowest quality parameters are rated 1 Repeating a computation 1 Go to Calculations gt MM2 gt Repeat MM2 Job 2 Change parameters if desired and click Run The computation proceeds MMFF94 Use MMFF94 to perform energy minimization calculations on proteins and other biological structures Multiple processors Molecular modeling force field calculations can become time consuming and impractical for large molecules You can overcome this problem by using multiprocessors To verify that multiple processors are being used Go to Calculations gt MMFF94 gt Perform MMFF94 minimization Chapter 6 Computational Engines 92 of 318 ChemBio3D 14 0 Perkin For the Better In the Preferences tab select Enable Multiprocessor support Displaying
78. 0 0 12 0 0 r 0 0 2 1 0 r c 3 C 1 53523 1 111 7747 N w cia C 1 53973 1 109 7114 1 SS 6989 1 1 The internal coordinates section of the MOPAC Data File format contains one line of text for each atom in the model Each line contains bond lengths bond angles dihedral angles action integers and connectivity atoms As shown in the illustration above C 1 is the origin atom C 2 is connected to C 1 with a bond of length 1 54152 A C 3 is connected to C 2 with a bond of length 1 53523 A and is at a bond angle of 111 7747 degrees from C 1 C 4 is connected to C 1 with a bond of length 1 539734 A and is at a bond angle of 109 711411 degrees from C 2 C 4 also forms a dihedral angle of 55 6959 degrees with C 3 The action integers listed next to each measurement are instructions to MOPAC 1 Optimize this internal coordinate 0 Do not optimize this internal coordinate 1 Reaction coordinate or grid index When you create a MOPAC file in ChemBio3D an action integer of 1 is assigned to each non zero bond length bond angle and dihedral angle for each atom record in the file FORTRAN Formats The description of the MOPAC Data File format for each line is Chapter 14 File Formats 242 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 1 Keywords for Calculation Instructions E femmes ee Internal coordinates for molecule Blank line terminates geometry Yes definition The FORTRAN for
79. 0 729 2 197 2 7422 1 5961 0 7156 0 8718 0 004 2 7422 Chapter 14 File Formats 225 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Alchemy file format 7 Note Alchemy III is a registered trademark of Tripos Associates Inc Each line represents a data record containing one or more fields of information about the molecule The fields that ChemBio3D uses are Line 1 contains two fields The first field is the total number of atoms in the molecule and the second field is the total number of bonds Lines 2 20 each contain five fields of information about each atom in the molecule The first field is the serial num ber of the atom the second field is the atom type the remaining fields are the X Y and Z coordinates 7 Note You can modify and create atom types in the Alchemy file format See Editing file format atom types on page 224 for instructions a Lines 21 40 describe the bonds in the molecule The first field is the bond number ranging from 1 to the number of bonds the second field is the serial number of the atom where the bond begins the third field is the serial number of the atom where the bond ends and the fourth field is the bond type The possible bond types are SINGLE DOUBLE TRIPLE AMIDE or AROMATIC Note that all the bond order names are padded on the right with spaces to eight characters FORTRAN The FORTRAN format for each record of the Alchemy file
80. 000 3D rotation matrix 1 000 0 000 0 000 0 000 1 000 0 000 0 000 0 000 1 000 3D scale factor 2D scale factor 2D attributes 1o00000000000000 3D attributes o0000000000 Global display attributes 101 12 256 Atom List Atom Lbl Type x y x y z bits chrg ichrg frag istp lp chrl ring frad name seg grp FLAGS Chapter 14 File Formats 237 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better 000000 Cc 0000000C40 1000000 0 5 0 000000 Bond List Bond bond type atoml atom2 cis trans length locked ring Sh_nr Qorder Qtopol Qs 0 000 0000 S 00 0 000 0000 S 00 Chapter 14 File Formats 238 of 318 ChemBio3D 14 0 PerkinElme For the Better 14 Is 000 11145 000 12 1 4 11 000 13 1 4 12 000 14156 000 0000 15 0 000 0 0 0 0 S 0 0 16 1 5 10 000 0000 17167 000 0000 18 16 13 000 0000 1917 8 000 0000 Bond Angles bondl bond2 angle locked Dihedral Angles atl cons atl at2 at2 cons angle locked Planarity data User data area End of File MkII The MSI MolFile format is broken up into several sections Section headers are preceded by a Blank lines also a contain a Each line is either a blank line a header line or a data record containing one or more fields of information about the structure Individual fields are delimited by space s or a tab The fields in th
81. 1 C 2 is connected to C 1 the origin and distance defining atom by a bond of length 1 54146 A C 3 is connected to C 2 with a bond of length 1 53525 A and at a bond angle of 111 7729 degrees with C 1 defined by C 3 C 2 C 1 C 4 is attached to C 1 with a bond of length 1 53967 A and at a bond angle of 109 7132 degrees with C 2 defined by C 4 C 1 C 2 C 4 also forms a dihedral angle of 55 6959 degrees with C 3 defined by C 4 C 1 C 2 C 3 This portion of the Internal coordinates file for C 1 through C 4 of Cyclohexanol can be represented by the following structural diagram FORTRAN formats The FORTRAN formats for the records in an Internal coordinates file are as follows Line Number Description FORTRAN Format oomen os Second Atom 14 1X 13 1X F9 5 Fourth Atom to Last Atom 14 3 1X 13 1X F9 5 14 14 2 1X 13 Third Atom 1X F9 5 Chapter 14 File Formats 231 of 318 ChemBio3D 14 0 PerkinE E For the Better Blank Line Ring Closure Atoms MacroModel MacroModel is produced within the Department of Chemistry at Columbia University New York N Y The Mac roModel file format is defined in the MacroModel Structure Files version 2 0 documentation The following is a sample file that describes a model of cyclohexanol cyclohexanol 396 0 3501 1 055 455 0 740 1 587 SLI 1 222 0 497 302 0 048 0 10 372 1 0566 0 62 606 1 5251 0 459 068 083 0 2
82. 13 The Output box _ Note The values of the energy terms can vary slightly based on the type of computer processor you are using The steric energy for the eclipsed conformation 3 9 kcal mole is greater in energy than that of the staggered con formation 1 kcal mole indicating that the staggered configuration is the conformation that is more likely to exist Chapter 17 Tutorials 298 of 318 ChemBio3D 14 0 PerkinE For the Better Tutorial 5 The Dihedral Driver The dihedral driver graphs the conformational energy of a model by varying up to two dihedral angles that you select At each dihedral angle value the model energy is minimized using the MM2 force field and the steric energy of the model is calculated and graphed After the calculation is complete you can view the data to locate the conformations with the lowest steric energy values and use these as starting points for further refinement in locating a stationary point In this tutorial we demonstrate a single angle plot using the dihedral driver on ethane 1 Build a model of ethane 2 Select the carbon carbon bond 3 Go to Calculations gt Dihedral Driver gt Single Angle Plot The Dihedral Driver Chart opens When the calculation is complete a graph displays the energy versus the angle of rotation around the selected bond To view the conformation 1 Inthe chart click any point along the curve The dihedral bond in the model rotates the angle you select in the
83. 18A respectively To precisely reproduce the energies obtained with Allinger s force field set the cutoff constants to large values 99 for example in the MM2 Constants table OOP bending Atoms that are arranged in a trigonal planar fashion as in sp2 hybridization require an additional term to account for out of plane OOP bending MM2 uses the following equation to describe OOP bending E K 6 SF 8 Out of Plane The form of the equation is the same as for angle bending however the 6 value used is angle of deviation from coplanarity for an atom pair and 9 is set to zero The special force constants for each atom pair are located in the Out of Plane bending parameters table The sextic correction is used as previously described for Angle Bending The sextic constant SF is located in the MM2 Con stants table Pi bonds and atoms with pi bonds For models containing pi systems MM2 performs a Pariser Parr Pople pi orbital SCF computation for each system A pi system is defined as a sequence of three or more atoms of types which appear in the Conjugate Pi system Atoms table Because of this computation MM2 may calculate bond orders other than 1 1 5 2 and so on F Note The method used is that of D H Lo and M A Whitehead Can J Chem 46 2027 1968 with heterocycle parameter according to G D Zeiss and M A Whitehead J Chem Soc A 1727 1971 The SCF computation yields bond orders which are used to scale
84. 22 2 tere ech ole Bs ghoul a neste Ge Se acess cea ee ee eee 181 Why use ChemSenpt Joc So oe Stal oe tee Ais aa eh Seah DS teens oda bs Meee aY 181 How ChemScript works 22 22 2222 eee eee ccc eee e cece ccc ence cece cece cence DDIAD DDALL Daar anonra 182 Getting Started 22000 c cece cece cece cece cece cece cece cece cece eeeeeeeeceseeeteteteteeesneeees 182 Editing Scripts 0 0000 0000000000000 aa e cece eee ALA ce cece cece ec eeeeeeeceeceeeeeeeeeeeees 183 Introducing the ChemScript API 2 2 e cece eee e cece cece ceececeeececeeeeeees 184 BIL a ee PEN Ce EE PT ree Se Poe ee 185 USETUNRETETENCES ae fas oe sash tree ete A a ae ee Aa ate a eee 188 Table of Contents V ChemBio3D 14 0 Perkin For the Better Chapter 11 Chemical properties _ 2 2 22 2 ccc ccc eee cece eee e cece eceeeeeeeeeees 189 ChemBio3D properties 2 2 20 ooo e cece ec ce ccc cc cee cence ccecccceecececeeccccccceercececccceceeneeeece 189 ChemBioFinder properties 2 2 22 ccc cece c cece cece ec cece eee ce eee ceceeeeeeececeeeceeeeeeeeeeeseseees 216 ChemBioDraw properties 2 2 2 22 2 ccc cee c ccc e cece cece cece eee c cece cece eee ee ee ce ceeeeeeeeeeessseeeees 217 ChemDraw Excel properties 2 22 2 0 22 2 cc cence cece cece cece eee e eee ceeeeeeeeeeeeeeceeeeeeeees 217 Chapter 12 Keyboard modifiers _ 0000000000 occ ccc cece cece cee cece eee eeeeeeeeeeeeeeeeeeees 218 Poa ccs st
85. 3D to resize the model then save 3DM The QuickDraw 3D MetaFile 3DM file format contains 3 dimensional object data describing the model You can import 3DM files into many 3D modeling applications You can transfer 3DM files between Macintosh and Windows platforms AVI Use this file format to save a movie you have created for the active model You can import the resulting movie file into any application that supports the AVI file format Chapter 14 File Formats 259 of 318 ChemBio3D 14 0 PerkinElmer For the Better Export formats The following file formats are used to export models to chemistry modeling application other than ChemBio3D0 Most of the formats also support import Alchemy Use the ALC file format to interface with TRIPOS applications such as Alchemy This is supported only for input Cartesian Coordinates Use Cartesian Coordinates 1 CC1 or 2 CC2 to import or export the X Y and Z Cartesian coordinates for your model When you save a file as Cartesian Coordinates an option button appears in the Save As dialog box To specify the save options 1 Click Save As 2 Select Cartesian Coordinate format cc1 or cc2 in the Save As dialog box 3 Select from these options By Serial Number Contain a connection table for each atom with serial numbers By Position Contain a connection table for each atom that describes adjacent atoms by their positions in the file Missing Not contain a connection
86. 77 053 603 1 968 27 340 2 451 e222 972 0 925 058 742 0 30 972 0 679 960 0 92 981 0 99 309 0 037 033 15272 052 1 881 215 2 41 Each line represents a data record containing one or more fields of information about the model Each field is delimited by space s or a tab Line 1 contains two fields The first field is the number of atoms in the model the second field is the name of the molecule The molecule name is the file name when the file is created using ChemBio3D 1 Lines 2 19 each contain 17 fields describing information about one atom and its attached bond Chapter 14 File Formats 232 of 318 ChemBio3D 14 0 PerkinElmer For the Better B 3 1 1 5 1 16 1 17 1 O 0 0 0 0 606 1 5251 0 459 0 l A Cc D E Figure 14 3 In the MacroModel file format each row describes the location and attachments for an atom A The atom type for the atom B The atom pairs for the atoms that are bonded C The first number of each atom pair is the serial number for the bonded atom the second number is the bond type used D The X Y and Z coordinates of the atom E the atom color 7 Note ChemBio3D ignores atom colors This color field will contain a zero if the file was created using ChemBio3D 7 Note Atom types are user definable See Editing file format atom types on page 224 for instructions on modi fying or creating an atom type FORTRAN Formats The FORTRAN format for e
87. 81 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Assigning building types The easiest way to build models is to allow ChemBio3D 14 0 to assign building types to atoms as you build To allow building types to be assigned as you build 1 Go to File gt Model Settings The Model Settings dialog box appears 2 Inthe Model Settings dialog box select the Model Building tab 3 Select the Correct Building Type check box 4 Click OK If the Correct Building Type check box is selected building types are corrected when you add delete or replace atoms or bonds Example 1 Build a methane model as shown 2 Click the Build from Text tool 3 Click a hydrogen atom A text box appears as shown below 4 Type C in the text box and press ENTER If the Correct Building Type check box is selected this figure appears Chapter 5 Building Advanced Models 82 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 If the Correct Building Type check box is not selected this figure appears As depicted in the above example when building types are assigned and you replace atoms ChemBio3D attempts to assign the best type to each atom by comparing the information about the atom such as its symbol and the number of bonds to each record in the Atom Type table In addition the building types of pre existing atoms may change when you replace atoms of one type with other atoms of a different type Defining bui
88. A color palette opens 2 Inthe color palette choose the color you want and click OK Model explorer The model explorer lets you explore the structural features of the model By default the model explorer is collapsed and appears as a vertically aligned tab When you hover the mouse over the model explorer tab the model explorer window appears and displays a hierarchical tree representation of the currently displayed model Model Explorer ax S F teenie C1 C 2 C 3 C 4 C 5 C 6 0 H 8 H 3 H 10 H 11 H 12 H 13 Using the Model Explorer window you can alter the model properties The changes you make to a group are applied to all members in the group The hidden or changed features are marked with colored icons so you can track your modifications For more inform ation see Model Explorer on page 51 User interface preferences You can change the user interface style and behavior to suit the way you work You can change the GUI color scheme tab behaviors and other display options To change the settings 1 Go to File gt Preferences The Preferences dialog box appears 2 Click the GUI tab 3 Choose a style in the GUI Style section to change the overall look and feel of the ChemBio3D interface f Note The VS 2005 Whidbey style option includes smart docking for toolbars 4 Click Apply to view the new settings To return to the default style setting click Reset to Default 5 Enable or d
89. AMESS Interface and select Internal Energy 3 Click OK lonization Potential The ionization potential is the energy needed to remove electrons from an atom To calculate ionization potential using Gaussian 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select lonization Potential 3 Click OK Chapter 11 Chemical properties 200 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 An alternative method 1 Go to Calculations gt Gaussian Interface gt C ompute Properties 2 Inthe Properties tab select lonization Potential and click Run The results appear in the Output window Kinetic Energy The formula to calculate kinetic energy is K p gt 2m Where K is the kinetic energy mis the mass and p is the momentum which is the product of mass and velocity v To calculate kinetic energy using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Kinetic Energy 3 Click OK An alternative method 1 Go to Calculations gt GAMESS Interface gt Compute Properties 2 Inthe Properties tab select Kinetic Energy and click Run Lipinski Rule of five Reports the values necessary to determine the Lipinski rule of five molecular weight number of HBond acceptors a number of HBond donors number of rotatable bonds LogP To report the Lipinski rule of five 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and sel
90. C input file MOPAC graph gpt Chapter 14 File Formats pP PerkinElmer For the Better 256 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better Protein Data Protein DB Bank Standard Molecu SMD File smd lar Data SYBYL MOL SYBYL SYBYL MOL2 SYBYL2 To save a model with a different format name or location 1 Go to File gt Save As The Save File dialog box appears 2 Specify the name of the file the folder and where you want to save the file 3 Select the file format in which you want to save the model 4 Click Save When you save a file in another file format only information relevant to the file format is saved For example you will lose dot surfaces color and atom labels when saving a file as an MDL MolIFile Publishing formats The file formats described in this section are available for importing and exporting models as pictures The pictures can then be used in desktop publishing and word processing software Image format features a Transparent OLE copy paste a Save bitmap images up to 1200 DPI a JPEG Quality compression can be adjusted from 0 to 100 a Movies can be saved in animated GIF multi page TIFF or AVI formats The defaults are set in the new Pictures tab of the Preferences dialog box The Save As dialog box now displays the available options to make it easier to override defaults when you save Chapter 14 File Formats 257 of 318 hemBio3D 14 I ChemB
91. CTRL key at the same time To deselect a selected atom or bond click the atom in the model explorer while pressing the CTRL key Chapter 4 Displaying Models 53 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better Selecting by distance You can select atoms or groups near a selected atom or group of objects This feature is useful for among other things highlighting the binding site of a protein To select atoms or groups by distance 1 Select an atom or fragment using the model explorer 2 Right click the selected object From the context menu point to Select and click an option a Select Atoms within Distance of Selection selects all atoms within the specified distance from any part of the current selection a Select Groups within Distance of Selection selects all groups with one or more atoms within the specified dis tance from any part of the current selection Select Atoms within Radius of Selection Centroid selects all atoms within the specified distance of the centroid of the current selection a Select Groups within Radius of Selection Centroid selects all groups with one or more atoms lying within the specified distance of the centroid of the current selection _ Note Atoms or groups already selected are not included Also the current selection will be cleared unless mul tiple selection is used Hold the SHIFT key down to specify multiple selection Selecting object color By default all atoms are assigned a colo
92. ChemBio3D To adjust the size of a copied molecule resize the model window before you copy it Tip To export copies of several models so that they are all the same size adjust the model windows so that they are the same size and ensure that Fit Model to Window is on To tum on the Fit Model to Window feature go to File gt Model Settings gt Model Building tab and select the Fit Model to Window check box Copying to ChemBioDraw Models that you copy to ChemBioDraw appear as 2D drawings This means that you can edit a drawing as you would any other ChemBioDraw structure To copy a model into ChemBioDraw 1 Select the model Chapter 3 Basic Model Building 29 of 318 hemBio3D 14 I HnemBiog 9 PerkinElmer For the Better 2 Go to Edit gt Copy As gt ChemDraw Structure 3 In ChemBioDraw go to Edit gt Paste Copying as simple notation To copy the model as a SMILES InChl or InChiKey string select the model and go to Edit gt Copy As and choose either SMILES InChl or InChIKey Embedding The ChemBio3D ActiveX control lets you embed models in Microsoft PowerPoint Word HTML based documents or any COM aware application _ Note To see an embedded object of ChemBio3D in Microsoft Word you may need adjust the macro security set tings The macro security settings should be either Low or Medium with macros enabled When a model is embedded you can view it using many of the features found in ChemBio3D For example you can rot
93. ChemBio3D reconciles the actual distance between atoms in two fragments to their optimal distances by rigidly moving one frag ment relative to the other Removing measurements You can remove information from the Measurement table without affecting the model Go to Structure gt Meas urements gt Clear Displaying atom coordinates The coordinate tables display the position of each atom in your model The Internal coordinate table shows the pos ition of each atom relative to the position of another atom The Cartesian table displays the X Y and Z coordinates of each atom relative to a fixed position in space To display the Internal coordinates table go to View gt Cartesian Table Internal coordinates Z Matrix coordinates The first atom in the internal coordinates table is defined as the origin atom All other atoms in the table are listed with their corresponding positions relative to the origin atom To display the internal coordinates table go to View gt Internal Coordinates Table Chapter 4 Displaying Models 60 of 318 ChemBio3D 14 0 Perkin For the Better When you select a record in the table the corresponding atom is selected in the model Conversely when you select atoms in the model the corresponding records are selected in the table To change which atom is the origin atom go to Structure gt Set Internal Coordinates gt Set Origin Atom Cartesian coordinates The fields in the Cartesian Coordinates table contain the
94. ChemBio3D 14 0 2 Click the down arrow on the Rotate tool S to open the rotation dial tool 3 Select the Y axis and drag the dial to show 55 Tip To get exactly 55 you may need to edit the value in the number box After editing press ENTER The value displayed in the right corner of the dial should be the same as in the number box The resulting model appears as shown below the second model may appear in a different position on your computer Figure 17 19 Aligning models Set optimal distances The Optimal distance determines how closely the molecules align In this tutorial you will set the distance to 5A 1 Inthe model explorer select C 6 in Fragment1 in the AA mon 2 group 2 Locate the C 98 atom in Fragment 2 AA mon 12 group and CTRL click to select it 3 Go to Structure gt Measurements gt Display Distance Measurement The C 98 C 6 atom pair appears in the measurement table 4 Click the Optimal cell 5 Type 5 and press ENTER The optimal distance between C 6 and C 98 is specified as 5 000A To have a reasonable align you must specify at least four atom pairs Repeat steps 1 through 5 for matching atom pairs throughout the fragments For example if you choose one pair from each group your list might look like this Note that the Actual values in the following table may differ oces 000 C 98 C 6 21 1840 5 0000 Chapter 17 Tutorials 304 of 318 Bio3D 14 I ChemBio3D 14 0 PerkinElmer For the
95. HUMAN HEALTH ENVIRONMENTAL HEALTH ChemBio3D 14 0 User Guide pP PerkinElmer For the Better hemBio3D 14 I Enema ere PerkinElmer For the Better Table of Contents Recent ACGIT ONS 2258 ose crete ele histo ee ec eae Be Oe hae ieee Cae aba EOS E ENEA ENEE aa EG viii Chapter 1 About ChemBio3D _ 2 2 2 2 2 022 22 c ee cece cece cece cece aaan naana 1 Additional computational engines 222 2222 e eee cece cece cece cece cece cece cece cece cece ee teeeeeeeeeeeeeeeeees 1 Serial numbers and technical support 2 2 22 cece eee cece eee eececccc cee eee AIDIA anaoa anaana an 3 About ChemBio3D Tutorials 2 2 22 2200 ee 3 Chapter 2 ChemBio3D Basics 2 2 2 2 coc ene ccc eee e cece cece eee eeeeecceceteeeeees 5 Gettingiaround 2 222 2 fet oe 2 522 dacs ctanneses seated eae seca dense oe ide woes ania ele he eee ee oak eee ade 5 User interface preferences 00 00022 c occ cee eee eee eee bee e cece eeeeeeceeeeeccececeeceeseeeees 9 Background settings 0000 000 cece eee cece cece cece cece cece cece cece cece ee ceceeeeceecececeeeeeeeeeeee 10 Sample files 2 2 20 000222 c cece cece cece cence cece cece eee eee e cece cece eeeee eee ceeeeeeeeeeeeeseeees 10 STALO KON DB Ke 0 00 Cac 10 Chapter 3 Basic Model Building 00 00 0000 o coco ccc ec eee ee cece cece eeeeeeeeeeeeeeees 12 Default settings 0 0 2 22 cece cece cece cece ccc ccc e cece cece ee eect eee e
96. IALO Bi bd t C o a Bie BZ Untitied 1 b gt x ChemBioDraw Livelink a x QO Oe Chem SMILES AP NUM SCR Figure 17 1 A 3D model of benzene To change the benzene ring to phenol 1 Select a bond tool in the Building toolbar 2 Double click any hydrogen in the 3D model A text box appears 3 Type OH use capital letters in the text box and press ENTER The phenol molecule appears in the Model window and in the ChemDraw panel Tutorial 2 Building with bond tools In this tutorial we use a model of ethane to demonstrate some fundamental ChemBio3D features We show how to rotate models view bond properties and add atom serial numbers First we build the ethane model Chapter 17 Tutorials 285 of 318 ChemBio3D 14 0 PerkinE For the Better 1 Click the Single Bond tool Jin the Building toolbar 2 Click drag in the Model window and release the mouse button A model of ethane appears since you have draw a single bond with default carbon atoms and default H placement Rotating models To see the three dimensional features of your model rotate it using the Rotate tool EMI You have a choice of rotat ing free hand around the X Y or Z axis or around a selected bond The status bar displays the angle of rotation To perform free hand rotation 1 Select the Rotate tool in the Building toolbar 2 Click drag near the center of the model window 7 Note The axis of rotation is determined by the d
97. In an energy minimization routine the Root Mean Square RMS of the derivative of the energy with respect to the Cartesian coordinates is used as a criterion to decide when to stop looking for a lower energy and accept the cur rent value as representing the minimum In theory the RMS gradient is zero when an energy minimum has been Chapter 6 Computational Engines 111 of 318 ChemBio3D 14 0 Perkin For the Better achieved however this is not possible to achieve practically Therefore a default value for the RMS gradient is set when setting up a geometry optimization The default value of 0 100 is a reasonable compromise between accuracy and speed Reducing the value means that the calculation continues longer as it gets closer to a minimum Increasing the value shortens the calculation but leaves you farther from a minimum Increase the value for a better optimization of a conformation that you know is not a minimum but you want to isolate it for computing comparative data To use a value lt 0 01 specify LET in the keywords section General Tab Wave Function Selecting a wave function involves deciding whether to use RHF or UHF computations a RHF is the default Hartree Fock method for closed shell systems To use RHF select the Close Shell Restric ted wave function UHF is an alternative form of the HF method used for open shell systems To use UHF select the Open Shell Unrestricted wave function To calculate Hyperfine Coupl
98. Inthe Minimize Energy dialog box click General 2 On the General tab set these options Chapter 6 Computational Engines 135 of 318 ChemBio3D 14 0 Perkin For the Better a Select the Solvation model Type the dielectric constant for the solvent The box does not appear for gas phase computations a Inthe Results In box type or browse to the path to the directory where results are stored a If desired add CS GAMESS keywords to the Additional Keywords dialog box Viewing and animating GAMESS IR vibrations After you create an infrared spectrum using GAMESS you can view and animate the IR modes in the Model Window To compute the IR spectrum 1 Draw the structure 2 Go to Calculations gt GAMESS Interface gt Predict IR Raman Spectrum The GAMESS Interface dialog box opens 3 Inthe dialog box click the Job amp Theory tab 4 Click Run The spectrum appears when the computation is done f Note The computation may take several minutes for larger models To animate the IR vibration 1 Click the IR Spectrum button on the Model Display toolbar The Animate IR vectors for model dialog box opens 2 Inthe dialog box select either the Frequency or the Intensity Mode The drop down list is sorted by the mode you select 3 Inthe drop down list select the frequency and intensity to use in the animation the first number in each number pair is for the mode you chose 4 Select from these options a Show Vectors
99. Is a graph index defined by n MTI E i 1 Where E are the components of the vector E A D d Where A is the adjacency matrix and D is the graph distance matrix and d is the vector of vertex degrees of a graph F Note An atom s degree is the number of non hydrogen atoms to which it is adjacent To calculate the molecular topological index 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Molecular Topological Index 3 Click OK Molecular Volume 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select Molecular Volume 3 Click OK An alternative method 1 Go to Calculations gt Gaussian Interface gt Compute Properties 2 Inthe Properties tab select Molecular Volume and click Run Chapter 11 Chemical properties 206 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Mulliken Charges The sum of Gross Orbital Population GOP terms over all basis functions on a given atom A is called the Gross Atom Population or GAP R Mulliken charge for atom A is expressed as Q4 Z GAP Where Za is the atomic number of atom A To calculate Mulliken charges using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Mulliken Charges 3 Click OK An alternative method 1 Go to Calculations gt GAMESS Interface gt C ompute Properties 2 Inthe Properties tab select Mulliken Charges and click Run The re
100. It also illustrates how you can read chemical data formatted as a SMILES string See Example 004 script py Example 5 Computing Canonical Codes This example script checks whether any structures appear in both of two SD files based on the structures canonical codes The output is anew SD file with the duplicate structures excluded See Example 005 script py Chapter 10 ChemScript 186 of 318 ChemBio3D 14 0 PerkinElmer For the Better This example first computes the canonical code for each structure Since the canonical code does not vary with dif ferent representations of the same chemical structure you can use it to determine whether two structures are chem ically equivalent This example also introduces the Python Dictionary which is an associative array The dictionary maps a key toa value The dictionary is used to determine whether a canonical code has been previously encountered This example uses an alternate looping construct to read an SD file Canonical codes should never be permanently stored because their representation can change among different versions of ChemScript Example 6 Structure Overlay This script introduces the ChemScript structure overlay feature It uses a scaffold structure file to superimpose two chemically similar structures The script first examines the structures in an SD file that contain a common scaffold substructure It then aligns these structures so that they have the same orientation
101. M2 Atom Types table Chapter 7 Parameter Tables 140 of 318 ChemBio3D 14 0 Perkin For the Better Text Text numbers determine which measurements apply to a given group of atoms in other parameter tables For example C Alkane has a building type number of 1 and O Alcohol has a building type number of 6 To determine the standard bond length of a bond between a C Alkane atom and an O Alcohol atom look at the 1 6 record in the Bond Stretching table Charge The charge of a building type is used when assigning building types to atoms in a model When atom information is displayed the charge always follows the atom symbol Charges can be fractional For example the charge of a carbon atom in a cyclopentadienyl ring is 0 200 ChemBio3D displays the formal charge that has been assigned to atoms and calculates the delocalized charge Both charges are displayed when applicable in the popup window when you hover over an atom Max Ring The maximum ring size field indicates whether the corresponding building type should be restricted to atoms found in rings of a certain size If this cell is zero or empty then this building type is not restricted For example the maximum ring size of C Cyclopropane is 3 Rectification Type The rectification type specifies the type of atom used to fill open valences Rectification atoms are added or deleted as you build your model To activate rectification go to File gt Model Settings On the Model Building tab
102. MMFF94 atom types You can display the MMFF94 atom types for your model without performing calculations The Atom Property table lists each atom its atom type and its charge To view the list of MMFF94 atom types in your model 1 Go to View gt Atom Property Table 2 Go to Calculations gt MMFF94 gt Set Up MMFF94 Atom Types and Charges Calculating potential energy You can calculate the potential energy of your model using MMFF94 without performing an energy minimization beforehand 1 Go to Calculations gt MMFF94 gt Calculate MMFF94 Energy and Gradient 1 Inthe dialog box click Run 2 Goto View gt Atom Property Table to view the results The non bonded energy represents the pair wise sum of all the energies of all possible interacting non bonded atoms It is the sum of van der Waals interactions and coulombic electrostatic interactions among the atoms Electrostatic calculations The electrostatic energy is a function of the charge on the non bonded atoms of a molecule their interatomic distance and a molecular dielectric expression that accounts for the attenuation of electrostatic interaction by the environment It deals with interactions between particles or atoms that are spatially close and interactions between atoms that are spatially distant from one another Three methods ares supported Exact Method Fast Multipole Method FMM Adaptive Tree Code ATC that approximate the electrostatic interactions and hence any cutoff metho
103. Note Chem3D Pro ignores the unused field and topology code These fields will contain zeros if the file was cre ated using Chem3D Pro Limitations The MDL MolFile format does not support non integral charges in the same way as Chem3D Pro For example in atypical MDL MolFile format file the two oxygens in a nitro functional group NO contain different charges 1 and 0 In ChemBio3D models the oxygen atoms each contain a charge of 0 500 FORTRAN formats The FORTRAN format for each record of the MDL MolFile format is as follows Chapter 14 File Formats 235 of 318 ChemBio3D 14 0 Perkin For the Better C C C C Number of atoms Number of bonds Atom coordinates atomic symbol 3F10 4 1X A2 513 Bond id from atom to atom and 6 1X 12 bond type MDL V3000 MolFile The extended V3000 molfile consists of a regular molfile followed by a single molfile appendix that contains the body of the connection table Ctab 7 Note The file is flagged with the V3000 instead of the earlier V2000 version stamp There are two other changes to the header in addition to the version a The number of appendix lines is always written as 999 regardless of how many there actually are The dimensional code is maintained more explicitly Thus 3D really means 3D although 2D will be interpreted as 3D if any non zero Z coordinates are found Unlike the V2000 molfile the V3000 extended Rgroup molfile has the same
104. OT 2 DOUBLET C l n where n 2 is the simplest case First excited quartet ROOT 2 QUARTET C l n where n 4 is the simplest case First excited sextet ROOT 2 SEXTET C l n where n 5 is the simplest case Second Excited State The second excited state is actually the third lowest state the root 3 for a given system Singlet Triplet Quintet To request the second excited state use the following set of keywords Second excited doublet ROOT 3 DOUBLET C l n where n 3 is the simplest case Second excited quartet ROOT 3 QUARTET C l n where n 4 is the simplest case Second excited sextet ROOT 3 SEXTET C l n where n 5 is the simplest case F Note If you get an error indicating the active space is not spanned use C 1 gt n for the simplest case to increase the number of orbitals available in the active space To see the states used in a C I calculation type MECI as an additional keyword The information is printed at the bottom of the out file Chapter 15 References 276 of 318 Bio3D 14 I enemBIga 1 PerkinElmer For the Better Excited State UHF Only the ground state of a given multiplicity can be calculated using UHF Sparkles Sparkles are used to represent pure ionic charges They are roughly equivalent to the following chemical entities tetramethyl ammonium potassium or cesium cation electron barium di cation 2 electrons borohydride halogen or nitrate anion minus electron sulfate oxalate di anion m
105. Office 2013 and Windows 8 1 for both 32 and 64 bit machines Support for GAMESS 09 ChemBio3D comes with GAMESS 09 installed For more information see CS GAMESS on page 133 Depiction and animation of GAMESS IR Vibrations After you compute an infrared spectrum you can view and animate the IR vibration modes and the vectors that are applied For more information see Viewing and animating GAMESS IR vibrations on page 136 Molecular Orbital Calculations using GAMESS 09 and MOPAC 2009 You can now calculate molecular orbitals using either GAMESS 09 or MOPAC 2009 By default PM6 is the basis set in the latest version of MOPAC Support for Gaussian 09 In addition to Gaussian 03 ChemBio3D also supports Gaussian 09 Gaussian can be pur chased from PerkinElmer Support for V3000 MolFile Format For both import and export 2D projections of 3D surfaces The volume slicing tool lets you view a two dimension cross section of almost any molecular surface This becomes quite useful for viewing the electron density at any location in your model You can slice through an orbital or an entire model in either the X Y or Z planes and adjust the location of the slice as desired For more information see Volume slicing on page 70 Saving to Dropbox ChemBio3D allows you to save to Dropbox for users with a Dropbox account You can upload and download files between your remote Dropbox folder and your local machine You can also use Dropbox to pass
106. P PerkinElmer For the Better ChemBio3D 14 0 Computation Concepts Computational chemistry overview Computational chemistry lets you explore molecules using a computer when a laboratory investigation may be inap propriate impractical or impossible Aspects of computational chemistry include a Molecular modeling Computational methods Computer Aided Molecular Design CAMD Chemical databases a Organic synthesis design Molecular modeling can be thought of as the rendering of a 2D or 3D model of a molecule s structure and properties Computational methods on the other hand calculate the structure and property data necessary to render the model Within a modeling program such as ChemBio3D computational methods are referred to as computation engines while geometry engines and graphics engines render the model ChemBio3D supports several powerful computational chemistry methods and extensive visualization options Computational methods overview Computational chemistry encompasses a variety of mathematical methods which fall into two broad categories Molecular mechanics Applies the laws of classical physics to the atoms in a molecule without explicit con sideration of electrons Quantum mechanics Relies on the Schr dinger equation to describe a molecule with explicit treatment of elec tronic structure Quantum mechanical methods can be subdivided into two classes Ab initio and Semi empirical ChemBio3D
107. PAC 2007 and MOPAC 2009 Potential energy functions MOPAC provides five potential energy functions MNDO PM3 PM6 AM1 and MNDO d All are SCF Self Con sistent Field methods Each function represents an approximation in the mathematics for solving the Electronic Schr dinger equation for a molecule Historically these approximations were made to allow ab initio calculations to be within the reach of available com puter technology Currently ab initio methods for small molecules are within the reach of desktop computers Larger molecules however are still more efficiently modeled on the desktop using semi empirical or molecular mechanics methodologies To understand the place that the potential energy functions in MOPAC take in the semi empirical arena here is a brief chronology of the approximations that comprise the semi empirical methods The first approximation was termed CNDO for Complete Neglect of Differential Overlap The next approximation was termed INDO for Intermediate Neg lect of Differential Overlap Next followed MINDO 3 which stands for Modified Intermediate Neglect of Differential Chapter 15 References 268 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better Overlap Next was MNDO which is short for Modified Neglect of Differential Overlap which corrected MINDO 3 for various organic molecules made up from elements in rows 1 and 2 of the periodic table AM1 improved upon MNDO markedly Finally the mo
108. PerkinElmer For the Better Optimize to transition state To optimize your model to a transition state use a conformation that is as close to the transition state as possible Do not use a local or global minimum because the algorithm cannot effectively move the geometry from that starting point Computing properties To specify the parameters for calculations to predict properties of a model 1 Go to Calculations gt Gaussian gt C ompute Properties The Gaussian Interface dialog box appears with the Prop erties tab selected 2 Select the properties to estimate 3 Click Run _ Note If you use Gaussian 09 calculations are done on the Gaussian interface and you need to close the Gaus sian 09 interface to view the results in ChemBio3D Job description file formats Job description files are like Preferences files they store the settings of the dialog box There are two types as described below JDT format The JDT format is a template from which job types may be derived The Minimize Energy and Compute Properties job types are read only examples of these JDF format The JDF format is for saving job descriptions Click Save in the dialog box to save modifications without a warning or confirmation dialog box Saving either format within the Gaussian Job folder adds it to the Gaussian submenu for convenient access Creating an input file You can create a Gaussian input file to run This becomes useful if you want to run the calcula
109. PerkinElmer For the Better The ChemBioOffice 2014 suite lets you determine more than 100 different chemical topological physical and ther modynamic properties This guide describes the properties you can calculate using ChemBio3D and lists the property functions that are available in other ChemBioOffice 2014 applications ChemBio3D properties The properties listed below can be calculated in ChemBio3D Ultra for ChemBioOffice 2014 For more information on a property and how to calculate it click its link below B Balaban Index Boiling Point 0 Cp Cv Cluster Count Connolly Accessible Area Connolly Molecular Area Connolly Solvent Excluded Volume Critical Pressure Critical Temperature Critical Volume D Dipole E Electron Density Electrostatic Potential Elemental Analysis Enthalpy Entropy Exact Mass F Formal Charge Frequencies G Gibbs Free Energy H Harmonic Zero Point Energy Heat Capacity Heat of Formation Henry s Law Constant Hyper Polarizability Hyperfine Coupling Con stants I Ideal Gas Thermal Capacity Internal Energy Ionization Potential K Kinetic Energy L Lipinski Rule of five LogP Partition Coefficient LogS Lowdin Charges Lowdin Populations M Mass Melting Point Mol Formula Mol Formula HTML Mol Refractivity Mol Weight Molecular Mass Molecular Surfaces Molecular Topological Index Molecular Volume Mulliken Charges Mulliken Populations m z Numb
110. S iEk Jer Where Chapter 11 Chemical properties 202 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 a Z is the nuclear charge Pis the electronic density matrix a S12 is the square root of the overlap matrix Summation i runs over all basis functions centered on atom k To calculate Lowdin charges using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Lowdin Charges 3 Click OK An alternative method 1 Go to Calculations gt GAMESS Interface gt Compute Properties 2 Inthe Properties tab select Lowdin Charges and click Run Lowdin Populations In the Lowdin approach the non orthogonal atomic orbitals are transformed to an orthogonal set The transformed orbit als x are given by i 1 2 Yem S kek a In Lowdin Population Analysis LPA the B and gross electron populations associated with fragment A are a 2 pa ol 2 GP ys PS vex aca c ys Ps acA GP GP G The spin density is given by a 8 SP GP GP To calculate Lowdin population using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Lowdin Populations 3 Click OK Chapter 11 Chemical properties 203 of 318 ChemBio3D 14 0 PerkinElmer For the Better An alternative method 1 Go to Calculations gt GAMESS Interface gt Compute Properties 2 Inthe Properties tab select Lowdin Populations and click Run This is the ma
111. The 1 5 bond type has a dipole of zero despite the fact that the carbon and hydrogen atoms on this bond have unequal electronegativity This approximation drastically reduces the number of dipoles to be computed and has been found to produce acceptable results Angle bending parameters These parameter tables provide standard bond angle values that ChemBio3D 14 0 uses to determine the angles of bonds between atoms of various atom types There are three angle bending parameter tables Applied when the central atom has four or fewer attach ments and the bond angle is not in a three or four membered ring Angle Bending Angle Bending Parameters Parameters xml 2 Memberca e Membere Applied in 3 membered rings Ring Angles Ring Angles xml PP g 4 Membered 4 Membered ne Ring Angles Ring Angles xml Applied in 4 membered rings ChemBio3D uses additional information to compute the angle bending portions of the MM2 force field for any bond angles in your model that occur in 3 and 4 member rings Each of these tables consists of the fields described below Angle Type This field contains the atom type numbers of the three atoms that create the bond angle For example angle type 1 2 1 is a bond angle formed by an alkane carbon bonded to an alkene carbon which is bon ded to another alkane carbon Notice that the alkene carbon is the central atom of the bond angle KB The KB or the angle bending constant contains a measure of the amount of e
112. The total time of the run is the Step Interval times the number of steps Heating Cooling Rate dictates whether temperature adjustments are made If the Heating Cooling Rate check box is checked the Heating Cooling Rate slider determines the rate at which energy is added to or removed from the model when it is far from the target temperature A heating cooling rate of approximately 1 0 kcal atom picosecond results in small corrections which minimally disturb the trajectory A much higher rate quickly heats up the model but an equilibration or stabilization period is required to yield statistically meaningful results To compute an isoenthalpic trajectory constant total energy deselect Heating Cooling Rate Target Temperature indicates the final temperature to which the calculation will run Energy is added to or removed from the model when the computed temperature varies more than 3 from the target temperature The computed temperature used for this purpose is an exponentially weighted average temperature with a memory half life of about 20 steps 5 Click Run 6 Optional Click Stop to end the computation before it is done Saving a Job The job type and settings are saved in a JDF file if you click Save As on the dialog box before running a computation You can then run these computations in a later work session Chapter 6 Computational Engines 102 of 318 Bio3D 14 I ChemBio3 0 PerkinElmer For the Better Starting th
113. To draw a structure using Draw gt 3D ADD 1 Specify the group name and group ID of the compound 2 Click the Draw gt 3D ADD icon If a structure with specified group name group ID combination exists a message appears prompting you to replace the existing structure in the model window with the new one To replace the existing structure click Yes The new structure replaces the existing structure in the model window and in the structure browser If the structure browser is currently activated the value is added to the structure browser If no structure with specified group name group ID combination exists the structure in the ChemDraw panel is added to the model window and the structure browser ChemDraw panel synchronization limits By default the LiveLink mode is available only for molecules of fewer than 200 atoms To change the default setting 1 Go to File gt Preferences The ChemBio3D Ultra Preferences dialog box appears 2 Click the ChemDraw tab 3 Specify the number of atoms in Atom Synchronization Limit 100 10000 4 Click Apply and click OK 7 Note A higher value in the Atom Synchronization Limit 100 10000 field slows down the drawing as large dia grams have to be generated Structure browser Using the Structure Browser you can browse through multiple structures stored in a file and view them in the model window As you browse through a model you can select in the structure browser which structures appear
114. Total v lt gt Figure 6 4 Output for eclipsed ethane model The dihedral angle in the Actual column becomes 0 corresponding to the imposed constraint The difference in energy between the global minimum Total previous calculation and the transition state Total this calculation is 2 50 kcal mole To further illustrate minimization delete the value from the Optimal column for the dihedral angle Then click the MM2 icon on the Calculation toolbar After the minimization is complete the angle is still 0 degrees This is an important consideration when applying MM2 minimization It uses first derivatives of energy to determine the next logical move to lower the energy However for saddle points transition states the region is fairly flat and the minimizer is satisfied that a minimum is reached If you suspect your starting point is not a minimum try setting the dihedral angle off by about 2 degrees and minimize again Cyclohexane In this example you compare the cyclohexane twist boat conformation and the chair global minimum To build a model of cyclohexane Chapter 6 Computational Engines 98 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better 1 Go to File gt New An empty model window appears 2 Select the Build from Text tool 3 Click in the model window A text box appears 4 Type CH2 CH2 5 and press ENTER i Caution While there are other perhaps easier methods of creating a cyclohexane model you
115. UMO options Select HOMO N 6 The pi bonding orbital surface appears Chapter 17 Tutorials 306 of 318 ChemBio3D 14 0 PerkinElmer For the Better Figure 17 21 Pi bonding orbital surface Note You may need to rotate the molecule to view the orbitals 3 To view the LUMO go to Surfaces gt Select Molecular Orbital and Select LUMO N 7 The pi antibonding orbital surface appears Figure 17 22 Pi antibonding orbital surface Tutorial 9 Mapping Surfaces This tutorial demonstrates Gaussian minimization and how to map calculated values to molecular surfaces for view ing You can perform the same minimization using extended Huckel calculations The allyl radical is a simple example of resonance enhanced stabilization Aon We Sou HC Figure 17 23 The allyl radical To examine radicals with spin density surfaces first create the allyl radical 1 Go to File gt New 2 Right click in an empty area of the ChemDraw panel go to View gt ChemDraw Panel if it is hidden and go to Structure gt Convert Name to Structure 3 Inthe Insert Structure text box type 1 propene and click OK A molecule of 1 propene appears 4 Inthe Model window select the H9 hydrogen using the Select tool Lal 5 Press DELETE A dialog box appears asking if you want to turn off rectification ChemBio3D knows that or this valency carbon atoms have four substituents 6 Click Turn Off Automatic Rectification The propene radic
116. Vis peaks Use the UV Vis Peaks table to view the intensity and position of the peaks in the GAMESS UV Vis spectrum To view the table go to View gt UV Vis peaks Click a row in the table to highlight the corresponding peak in the spec trum Tip Using the spectrum viewer you can view spectra produced by computational engines besides GAMESS Minimizing energy To perform a CS GAMESS Minimize Energy computation on a model 1 Go to Calculations gt GAMESS gt Minimize Energy The GAMESS Interface dialog box appears with the Job amp Theory tab displayed 2 Use the tabs to customize your computation See the following sections for details 3 Click Run Specifying calculation settings You can specify the combination of basis set and particular electronic structure theory using the Job amp Theory tab By default the settings on this tab are optimized for ab initio computations Chapter 6 Computational Engines 134 of 318 ChemBio3D 14 0 PerkinElmer For the Better For more detailed information on basis set see the BASIS section of the CS GAMESS documentation To specify the calculation settings 1 From the Method list choose a method 2 From the Wave Function list choose a function 3 From the Basis Setlist choose the basis set 7 Note To use a Method or Basis Set that is not on the list type it in the Additional Keywords section on the Gen eral tab For more information see Specifying electronic configuratio
117. Windows that support bitmaps EPS The PostScript file format saves models as encapsulated postscript file EPS EPS files are ASCII text files containing the scalable PostScript representation of a ChemBio3D picture You can open EPS files using other applic ations such as PageMaker You can transfer EPS files among platforms including Macintosh Windows and UNIX TIF The Tagged Image File Format TIFF contains binary data describing a bitmap image of the model TIFF is a high resolution format commonly used for saving graphics for cross platform importing into desktop publishing applic ations TIFF images can be saved using a variety of resolution color and compression options As TIFF images can get large choosing appropriate options is important When you save a file as TIF an option button appears in the Save As dialog box To specify the save options 1 Click Options PEG Quality DPI 30 S Color Space RG v C Freed Scale Ptceisif s Frames No Frame v Naber of Frames 2 5 Fie pane Urttied 1 it v Swembpe M Conve 1CxImage Copyright 2001 2004 David Pizzolato Chapter 14 File Formats 258 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better Figure 14 5 The TIFF Options dialog box 2 Choose a resolution The size of the file increases as the square of the resolution 3 Choose a color option store colors using computer monitor RGB Indexed style of color encoding use printing pre
118. able References xml contains information concerning the source for other parameters Use of the References table does not affect the other tables Two fields are used for each reference record the reference number and the reference description Number The reference number is an index by which the references are organized Each measurement also contains a reference field that should contain a reference number indicating the source for that measurement Description The reference description contains whatever text you want to describe the reference Journal ref erences or bibliographic data are common examples Bond stretching parameters The Bond Stretching Parameters table Bond Stretching Parameters xml contains information about standard bond lengths between atoms of various atom types In addition to standard bond lengths is information used in MM2 cal culations in ChemBio3D The Bond Stretching table contains parameters needed to compute the bond stretching and electrostatic portions of the force field for the bonds in your model The Bond Stretching Parameters record consists of these fields Bond Type KS Length Bond Dpl Quality and Reference Bond Type The Bond Type field contains the building type numbers of the two bonded atoms For example Bond Type 1 2 is a bond between an alkane carbon and an alkene carbon KS The KS or bond stretching force constant field contains a proportionality constant which directly impacts the s
119. ach record of the MacroModel format is as follows Description FORTRAN p Format number of atoms and molecule name 1X 15 2X A file name MDL MolFile The MDL MolFile format is defined in the article Description of Several Chemical Structure File Formats Used by Computer Programs Developed at Molecular Design Limited found in the Journal of Chemical Information and Com puter Science Volume 32 Number 3 1992 pages 244 255 _ Note MDL MACCS II is a product of MDL Information Systems Inc now owned by Dassault by way of Accel erys by way of Symyx The following is asample MDL MolFile file created using Chem3D Pro This file describes a model of cyclohexanol the line numbers are added for reference only cyclohexanol Chapter 14 File Formats 233 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better Chapter 14 File Formats 234 of 318 ChemBio3D 14 0 Perkin For the Better Each line represents either a blank line or a data record containing one or more fields of information about the struc ture Each field is delimited by a space s or a tab The fields in the MDL MolFile format used by Chem3D Pro are described below 1 Line 1 starts the header block which contains the name of the molecule The molecule name is the file name when the file was created using Chem3D Pro 2 Line 2 continues the Header block and is a blank line 3 Line 3 continues the Header block and is anoth
120. ain icons that offer shortcuts to many commonly used functions You can click drag the toolbars to anywhere on your screen Chapter 2 ChemBio3D Basics 5 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 ChemDraw panel Lets you create or modify drawings of your model in two dimensions Structure Browser Lets you browse through the list of structures and view each one in the Model window Model Explorer Displays a hierarchical tree representation of the model The model explorer is useful for working with complex molecules such as proteins Status bar Displays information about the active frame of your model and hidden atoms Output window Displays text results such as calculation results The Model window You build your models in the model window Each model file you open or create adds a new tab Select a tab to activ ate the model you want to view An asterisk next to the file name indicates that the file has not been saved since you last made changes to it 4 Grubbs 2nd Gen Catalyst c3xmi Insulin xmt gt Bnet 4 Figure 2 1 A model of insulin in the active tab The ChemDraw panel Using the ChemDraw panel you can draw 2D structure drawings and convert them to 3D models Alternatively you can build a 3D model and convert it to a 2D drawing that displays in the panel To activate the ChemDraw panel go to View gt ChemDraw Panel By default the panel opens on the right side of the screen You can a
121. aks Species that contain unpaired electrons are a Free radicals a Odd electron molecules Transition metal complexes Rare earth ions Triplet state molecules For more information see the MOPAC online manual This table contains the keywords sent to CS MOPAC and those you can use to affect this property Chapter 6 Computational Engines 119 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Sent to CS MOPAC if you choose Open Shell Unrestricted wave functions to specify the use of the Unrestricted Hartree Fock methods Hyperfine Sent to CS MOPAC to specify the hyperfine computation GEO OK Sent to CS MOPAC to override checking of the Z matrix MMOK Sent to CS MOPAC to specify Molecular Mechanics correction for amide bonds Use the additional keyword NOMM to turn this keyword off Spin density Spin density arises in molecules that include an unpaired electron Spin density data provides relative amounts of alpha spin electrons for a particular state Spin density is useful for accessing sites of reactivity and for simulating ESR spectra Two methods of calculating spin density of molecules with unpaired electrons are available RHF Spin Density and UHF Spin Density UHF spin density The UHF Spin Density removes the closed shell restriction In doing so separate wave functions for alpha and beta spin electrons are computed For more information see the MOPAC online manual This table contains the
122. al Bonds In this tutorial we illustrate how to calculate the rotational energy of a C C bond in biphenyl using the dihedral driver We run the dihedral driver twice first with the minimization energy turned on and then with the minimization energy turned off Building biphenyl We first need to build a model of biphenyl The easiest way is to use Name gt Struct 1 With the text tool selected click in the model window A text field appears 2 Inthe text field type biphenyl and press ENTER A model of biphenyl appears Calculating the dihedral driver The dihedral driver lets you map the conformational space of a model by varying either one or two dihedral angles we use one in this tutorial With minimization turned on the model energy is minimized at each dihedral angle value using the MM2 force field and the total energy of the model is calculated and graphed After the calculation is com plete you can view the data to locate the models with the lowest energy values and use these as starting points for further refinement in locating a stationary point To turn on the minimization 1 Go to File gt Preferences 2 Inthe Preferences window select the Dihedral Driver tab 3 Select the Enable Minimization checkbox 4 Click OK Chapter 17 Tutorials 315 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 For the dihedral driver calculation you must select a bond in your model For this tutorial we select the C C bond
123. al appears Gaussian is available only for ChemBio3D Ultra Chapter 17 Tutorials 307 of 318 ChemBio3D 14 0 PerkinElmer For the Better Figure 17 24 Propene radical model Next perform the minimization 1 Go to Calculations gt Gaussian Interface gt Minimize Energy Geometry 2 Inthe Routine tab set the method to PM3 and the wave function to U Unrestricted Open Shell 3 Set the Wave Function to U Unrestricted Open Shell 4 Also inthe Routine tab set the Spin Multiplicity to 2 Aspin multiplicity of 2 is required because the molecule is a radical One of the best ways to view spin density is by mapping it onto the Total Charge Density surface This lets you see what portions of the total charge are contributed by unpaired electrons or radicals To view spin density mapped onto the total charge density surface 1 Inthe Properties tab select Molecular Surfaces and Spin Density 2 Click Run When the calculation is finished select the Rotate tool gt oland rotate the model back and forth It should be com pletely planar Figure 17 25 Viewing the minimized model To complete this tutorial you need to adjust several surface settings For convenience activate the Surfaces toolbar Go to View gt Toolbars gt Surfaces Chapter 17 Tutorials 308 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 1 On the Surfaces toolbar click Surface ES and select Total Charge Density The icon changes to de
124. al vibrations are the usual subjects of molecular dynamics studies Molecular dynamics alters the values of the intramolecular degrees of freedom in a stepwise fashion The steps in a molecular dynamics simulation represent the changes in atom position over time for a given amount of kinetic energy The Molecular Dynamics command in the Calculations menu can be used to compute a molecular dynamics tra jectory for a molecule or fragment in ChemBio3D A common use of molecular dynamics is to explore the con formational space accessible to a molecule and to prepare sequences of frames representing a molecule in motion For more information on Molecular Dynamics See Computational Engines on page 88 Molecular dynamics formulas The molecular dynamics computation consists of a series of steps that occur at a fixed interval typically about 2 0 fs femtoseconds 1 0 x 10715 seconds The Beeman algorithm for integrating the equations of motion with improved coefficients B R Brooks is used to compute new positions and velocities of each atom at each step Each atom i is moved according to the following formula y Ay T vj AE 5a i a 49 8 Similarly each atom is moved for y and z where Xp Yp and z are the Cartesian coordinates of the atom v is the velo old city a is the acceleration aj is the acceleration in the previous step and At is the time between the current step and the previous step The potential energy and de
125. amics computation Model display will decrease the speed in this order Wire Frame lt Sticks lt Ball and Sticks lt Cylindrical Bonds lt Ribbons lt Space Fill and van der Waals dot surfaces lt Molecular Surfaces 2 To view measurements during the simulation do one of the following Go to Structure gt Measurements gt Generate All Bond Angles Go to Structure gt Measurements gt Generate All Bond Lengths 3 Inthe Measurements table select the desired measurements 4 Go to Calculations gt MMFF94 gt MMFF94 Molecular Dynamics The Molecular Dynamics dialog box appears 5 Enter the appropriate values Step Interval Specifies the time between simulation steps in femtoseconds fs The step interval must be less than 5 of the vibration period for the highest frequency normal mode 10 fs for a 3336 cm 1 H X stretch ing vibration Normally a step interval of 1 or 2 fs yields reasonable results Larger step intervals may cause the integ ration method to break down because higher order moments of the position are neglected in the Beeman algorithm Frame Interval Specifies the interval at which frames and statistics are collected A frame interval of 10 or 20 fs gives a fairly smooth sequence of frames and a frame interval of 100 fs or more can be used to obtain samples of con formational space over a longer computation Terminate After causes the molecular dynamics run to stop after the specified number of steps The total tim
126. ample 001 script py The script reads the CDX structure files from a source directory applies the cleanup feature to each structure and write the modified files to an output directory The original files remain unchanged NH NH VA a Figure 10 1 The structure cleanup script reads a structure file left and creates a new cleaned up structure file right This example uses the CDXML format Other formats such as MDL MOL may also be applied You can also force ChemsScript to use specific file formats for reading and writing data Example 2 Create an SD file This example illustrates how you can create an SD file from existing CDXML files You can find the script at Example 002 script py We begin with a list of CDXML files that each contain a chemical structure The list of files is hard coded into the ChemScript script When executed the script uses the SDFileWriter method to create an SD file that includes all the structures Example 3 Create a list of CDXML files This example illustrates how to read an SD file and write a list of CDXML files You can find the source file at Example 003 script py Example 4 Filter an SD file This example uses the atomByAtomSearch method to demonstrate a simple application of the atom by atom sub structure search in ChemScript The program reads an SD file and filters structures into one of two output SD files structures that contain a phenyl group and structures that don t
127. an der Waals interactions ChemBio3D uses a fifth order polynomial switching function so that the resulting force field is second order continuous Because the charge charge interaction energy between two point charges separated by a distance r is proportional to 1 r the charge charge cutoff must be rather large typically 30 or 40A The charge dipole dipole dipole and van der Waals energies which fall off as 1 r2 1 r and 1 r respectively can be cut off at much shorter distances for example 25A 18A and 10A respectively Fortunately since the van der Waals interactions are by far the most numerous this cutoff speeds the computation significantly even for relatively small molecules Pi Orbital SCF computation ChemBio3D determines whether the model contains any pi systems and performs a Pariser Parr Pople pi orbital SCF computation for each system A pi system is defined as a sequence of three or more atoms of types which appear in the Pi Atoms table window PIATOMS xml The method used is that of D H Lo and M A Whitehead Can J Chem 46 2027 1968 with heterocycle para meters according to G D Zeiss and M A Whitehead J Chem Soc A 1727 1971 The SCF computation yields bond orders which are used to scale the bond stretching force constants standard bond lengths and twofold torsional barriers A step wise overview of the process used to perform pi system calculations is as follows Chapter 15 References 267 of
128. andard measurement used in building models The constant 71 94 is a conversion factor to obtain the final units as kcal mole The result of this equation is the energy contribution associated with the deformation of the bond from its equilibrium bond length This simple parabolic model fails when bonds are stretched toward the point of dissociation The Morse function would be the best correction for this problem However the Morse function significantly increases computation time As an alternative cubic stretch and quartic stretch constants are added to provide a result approaching a Morse func tion correction The cubic stretch term allows for an asymmetric shape of the potential well allowing these long bonds to be handled However the cubic stretch term is not sufficient to handle abnormally long bonds A quartic stretch term is used to cor rect problems caused by these very long bonds With the addition of the cubic and quartic stretch term the equation for bond stretching becomes E reton 1942K I r C S r OS 44 4 Both the cubic and quartic stretch constants are defined in the MM2 Constants table To precisely reproduce the energies obtained with Allinger s force field set the cubic and quartic stretching constant to 0 in the MM2 Constants tables Angle bending energy E pong 0 02191418 py Ky 0 0 j Angles The bending energy equation is also based on Hooke s law The K parameter controls the stiffness of the
129. ank files is as follows Chapter 14 File Formats 245 of 318 ChemBio3D 14 0 Perkin For the Better Number ChemBio3D Hydrogen Bonds Atoms in cols 7 11 32 36 are Donors Salt Bridge Atoms in cols 7 11 have 42 46 No Negative Charge Hydrogen Bonds Atoms in cols 7 11 47 51 are Acceptors 52 56 Hydrogen Bonds Salt Bridge Atoms in cols 7 11 have 57 61 Positive Charge The FORTRAN formats for the records used in the Protein Data Bank file format are as follows Line Description FORTRAN Format COMPND COMPND 4X 60A1 ATOM ATOM 2X 15 1X A4 1X A3 10X 3F8 3 16X HETATM HETATM 15 1X A4 14X 3F8 3 16 X CONECT CONECT 515 30X Chapter 14 File Formats 246 of 318 ChemBio3D 14 0 I PerkinE For the Better ROSDAL The ROSDAL Representation of Organic Structures Description Arranged Linearly Structure Language 1 file format is defined in Appendix C Rosdal Syntax pages 91 108 of the MOLKICK User s Manual The Rosdal format is primar ily used for query searching in the Beilstein Online Database Rosdal format files are for export only The following is a sample Rosdal format file created using Chem3D Pro for cyclohexanol 1 2 3 4 5 6 1 6 2 7H 3 8H 4 9H 5 10H 6 11H 1 120 13H 1 14H 2 15H 3 16H 4 17H 5 18H 6 19H SMD The Standard Molecular Data 2SMD file file format is defined in the SMD File Format version 4 3 documentation dated 04 Feb 1987 The fo
130. any of the model display modes Go to View gt Model Display gt Show Atom Dots An example using a stick model is shown below Chapter 4 Displaying Models 36 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Figure 4 1 Viewing dot surfaces To show atom dots for only selected atoms 1 Inthe model window select one or more atoms 2 Right click one of the selected atoms 3 Inthe context menu go to Atom Dots gt Show Atom Dots To display dot surfaces by default on all atoms 1 Go to File gt Model Settings and select the Atom amp Bond tab 2 Inthe Atom Dot Surfaces section click the Show by Default check box 3 Use the Density slider to adjust the density of the dot surface and click Apply 4 Click OK Serial numbers Each atom in a model is assigned a unique serial number to distinguish it from all other atoms As a result you can identify each atom when viewing the model explorer or measurements table To view the serial numbers select one of these options a For individual atoms use the Select tool to point to the atom The serial number appears in the pop up information a Goto View gt Model Display gt Show Serial Numbers Serial numbers for all atoms are displayed a Goto File gt Model Settings gt Model Display tab and check the Show Serial Numbers check box Click Apply and then click OK a Click the Serial Number toggle on the Model Display Toolbar Reassigning serial numbers Serial numbers ar
131. ar Orbital tool on the Surfaces menu The orbital number appears in parentheses in the HOMO LUMO submenu Go to Surfaces gt Select Molecular Orbital to see the list of HOMO LUMO orbitals in the model Select the orbital you want to view You can specify the isocontour value for any computed MO surface using the Isocontour tool on the Surfaces menu The default isocontour value for a newly computed surface is the value you last specified for a previously computed surface If you have not specified an isocontour value the default value is 0 01 Total spin density The total spin density surface describes the difference in densities between spin up and spin down electrons in any given region of a molecule s space The larger the difference in a given region the more that region approximates an unpaired electron The relative predominance of spin up or spin down electrons in regions of the total spin density sur face can be visualized by color when total spin density is mapped onto another surface total charge density Entirely spin up positive value electrons are red entirely spin down negative blue and paired electrons neutral are white You can use the total spin density surface to examine the unpaired electrons of a molecule The surface exists only where unpaired electrons are present Viewing the total spin density surface requires that both spin density and molecular surfaces are calculated by CS MOPAC or Gaussian using an open shell wave f
132. arameter Tables 145 of 318 ChemBio3D 14 0 Perkin For the Better diethylamine is the XRH value of 107 7 because the central N has one attached hydrogen atom In this case the XR2 and XRH values for the 1 8 1 angle type are identical As in the N N N triethylamine example above the only attached non hydrogen atom is a lone pair XH2 XH2 is the optimal value of a bond angle where the central atom of that bond angle is also bonded to two hydrogen atoms For example the optimal value of the 1 1 3 angle type for propionic acid is the XH2 bond angle of 110 0 since the central carbon C 2 has two attached hydrogen atoms Conjugated Pisystem bonds ChemBio3D uses the parameters in the Conjugated Pisystems Bonds table Conjugated PI System Bonds xml to correct lengths and angles of bonds that are part of a pi system ChemBio3D uses additional information to calculate the pi system portions of the MM2 force field for the pi bonds in a model There are five fields in records in the Pi Bonds table Bond Type dForce dLength Quality and Reference Bond Type The Bond Type describes the atom type numbers of the two bonded atoms For example bond type 2 2 is a bond between two alkene carbons d Force The dForce is a constant used to decrease the bond stretching force constant of a particular conjugated double bond The force constant Kx for a bond with a calculated pi bond order x is K K 1 x dForce where K is
133. arges Yes Yes with Molecular Electrostatic Potential map No Yes Total Spin Density Yes Molecular Electrostatic Potential No Yes Molecular Orbitals Yes Yes To display a surface 1 Perform a suitable calculation using Extended Huckel or Gaussian 2 Include the Molecular Surfaces property calculation whenever it is available _ Note Gaussian surfaces calculations are only available for ChemBio3D Ultra Calculation types Different calculation types can provide different results If you have performed more than one calculation on a model for example both an Extended Hutckel and an AM1 calculation you must choose which calculation to use when gen erating the surface To choose a calculation type 1 Go to Surfaces gt Choose Calculation Result and select one of your calculations 2 Goto Surfaces gt Choose Surface and choose a surface types F Note The Choose Surface commands are toggle switches Click once to display click again to turn off the display You can display more than one surface at a time When a surface is displayed its icon is highlighted 3 Adjust the display using the surface display tools O Tip If you make a lot of adjustments to the display activate the Surfaces toolbar and tear off the specific tools you will be using often Not all surfaces can be displayed from all calculations For example a Molecular Electrostatic Potential surface may be displayed only following a Gaussian or CS MOPAC calcula
134. at is open in ChemBio3D 3 Defining groups In this step named groups of atoms may be defined that are used in a post docking analysis Poses are analyzed to see if they do or do not interact with the named groups These groups are especially useful to quickly determine if a pose makes a key interaction with the receptor This is an optional step 4 Preparing GPF In this step you prepare the Grid Parameter File GPF GPF is used to specify the files and para meters used in the calculation Specifically the docking cavity s location and size are defined in this step 5 Preparing DPF In this step you prepare the Docking Parameter File DPF DPF is used to specify the files and parameters used for the docking calculation Specifically the parameters of the genetic search algorithm are defined in this step 6 Docking In this step you perform the docking calculation After you perform the docking calculation you can view the docking results using the AutoDock Results option under Calculations gt AutoDock Interface Step 1 Preparing the receptor You first load the receptor The receptor may be either in a file or a model that is already open in ChemBio3D After ward you use AutoDock to determine the charges and atom types throughout the molecule Note AutoDock accepts only molecules that it perceives as macromolecules These are generally proteins or polypeptide sequences that consist of standard residues To prepare the rec
135. ate the model zoom in and out and change its display mode To embed a model 1 InChemBio3D type CTRL A to select the model 2 Goto Edit gt Copy As gt Embedded Object 3 Launch the other application such as PowerPoint 4 To paste the object in the target document type CTRL V _ Note To view an embedded model in PowerPoint go to PowerPoint and press F5 to begin the slide show Qemtttemeeton Yewdedded 34 wanted han Embedded 3D Model Demo Figure 3 2 A ChemBio3D model embedded in FrontPage _ Note Modifying the embedded image in HTML is beyond the scope of this document If you are a programmer developing 3D modeling HTML pages see ReadMeC3DP htm in the ChemBio3D application folder When you embed a model in a PowerPoint presentation you can modify the display properties Select Properties from the context right click menu Listed below are the properties you can change in an embedded object Chapter 3 Basic Model Building 30 of 318 ChemBio3D 14 0 PerkinElmer For the Better AutoRedraw By default this is set to True DemoAxis Defines the axis of rotation when you select DemoRock or DemoSpin as a DemoMode DemoMode Determines whether the model rocks rotates or remains static in the slideshow DemoSpeed The relative rotation speed when the DemoMode is set as either DemoRock or DemoSpin EncodeData Cannot be changed By default this is set to True Fullscreen Cannot be changed By default this is se
136. ates the structure is hidden a agray box indicates the structures is selected The selected structure is always in view Tip To copy all fragments right click in the structure browser and select Auto populate the Structure Browser Note If you delete the fragment in the model explorer the fragment is also removed from the structure browser Fast overlay To overlay all objects right click in the structure browser and select Fast Overlay The fragments in the structure browser are overlayed MM2 calculations You can run simple MM2 calculations on fragments listed in the structure browser Calculations can only be run on one fragment at a time To perform an MM2 minimization on a fragment right click the fragment and select MM2 Minimization You can also simulate the rotational and translational kinetic energy in fragments over a range of temperatures Right click the fragment and select MM2 Dynamics The results of the simulation are listed in the Output window Display options To change the display mode for a fragment 1 Right click the fragment in the structure browser 2 Inthe context menu go to Display Mode and select display mode option For more information see Display modes on page 34 Color To apply the same color to all atoms in a fragment Chapter 2 ChemBio3D Basics 8 of 318 ChemBio3D 14 0 PerkinElmer For the Better 1 Right click the fragment in the structure browser and go to Color gt Select Color
137. ation method and a C 1 cal culation to correct the final RHF energies To see the states used in a C I calculation type MECI as an additional keyword The information is printed at the bottom of the out file Ground State UHF For UHF computations all unpaired electrons are forced to be spin up alpha Singlet ground state the most common configuration for a neutral even electron stable organic compound No additional keywords are necessary a UHF will likely converge to the RHF solution for Singlet ground states Triplet or Quintet ground state Use the keyword TRIPLET or QUINTET f Note When a higher multiplicity is used the UHF solution yields different energies due to separate treatment of alpha electrons Excited State RHF First Excited State The first excited state is actually the second lowest state the root 2 fora given spin system Singlet Triplet Quintet Chapter 15 References 275 of 318 ChemBio3D 14 0 PerkinElmer For the Better To request the first excited state use the following sets of keywords First excited Singlet ROOT 2 OPEN 2 2 SINGLET or specify the single keyword EXCITED First excited triplet ROOT 2 OPEN 2 2 TRIPLET C l n where n 3 is the simplest case First excited quintet ROOT 2 OPEN 4 4 QUINTET C l n where n 5 is the simplest case Second Excited State The second excited state is actually the third lowest state the root 3 for a given system Singlet Triplet Qui
138. ations gt Compute Properties 2 Expand GAMESS Interface and select Total Energy Chapter 11 Chemical properties 214 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 3 Click OK An alternative method 1 Go to Calculations gt GAMESS Interface gt C ompute Properties 2 Inthe Properties tab select Total Energy and click Run The results appear in the Output window 3 Click Run The results appear in the Output window Total Valence Connectivity Is the valence connectivity considered over all the heteroatoms To calculate the total valence connectivity 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Total Valence Connectivity 3 Click OK Vapor Pressure Is the pressure exerted by a vapor in equilibrium with its solid or liquid phase Vapor pressure measures the con centration of solvent molecules in the gas phase Vapor pressure can be calculated using Raoult s law The formula to calculate vapor pressure is Prot gt PiX 7 Where p is vapor pressure i is a component index and y is a mole fraction To report the vapor pressure 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Vapor Pressure 3 Click OK Water Solubility Is the maximum amount of a substance that can be dissolved in water at equilibrium at a given temperature and pres sure Water solubility is measured in mg L To report the water solubility
139. atom has three independent variables x y Z coordin ates visualizing a surface for a many atom model is impossible However you can generalize this problem by examining any two independent variables such as the x and y coordinates of an atom The main areas of interest on a potential energy surface are the extrema as indicated by the arrows a Global minimum The most stable conformation appears at the extremum where the energy is lowest A molecule has only one global minimum Local minima Additional low energy extrema Minima are regions of the PES where a change in geometry in any direction yields a higher energy geometry a Saddle point A stationary point between two low energy extrema A saddle point is defined as a point on the poten tial energy surface at which there is an increase in energy in all directions except one and for which the slope first derivative of the surface is zero Note At the energy minimum the energy is not zero the first derivative gradient of the energy with respect to geometry is zero All the minima on a potential energy surface of a molecule represent stable stationary points where the forces on each atom sums to zero The global minimum represents the most stable conformation the local minima less stable con formations and the saddle points represent transition conformations between minima Single point energy calculations Single point energy calculations can be used to calculate prop
140. atom must match these type characteristics for ChemBio3D to assign the building type to the atom a The atomic symbol a The bound to type if specified for the building type a The bound to order if the bound to type is specified The number of double triple and delocalized bonds F Note For comparing bond orders a building type that contains one double bond may be assigned to an atom that contains two delocalized bonds such as in benzene If the maximum ring size field of a building type is specified then the atom must be in a ring of that size or smaller to be assigned the corresponding building type If an atom is bound to fewer ligands than are specified by a building type geometry but the rectification type is spe cified then the atom can be assigned to that building type Open valences are filled with rectification atoms For example consider the building types for the structure of ethanoic acid Chapter 5 Building Advanced Models 80 of 318 ChemBio3D 14 0 PerkinElmer For the Better O 3 matches the criteria specified for the building type O Carbonyl Specifically it is labeled O it is bound to a C car bony by a double bond and it is attached to exactly one double bond and no triple bonds If an atom can be assigned to more than one building type building types are assigned in this order 1 Building types whose bound to types are specified and are not the same as their rectification types 2 Build
141. aves the results in the AutoDock work folder _ Note The file is saved in the AutoDock work folder in pdbqt file format and the default file name will be of the format lt InputFileName gt pdbqt For example if ligand mol2 is the input file that you have imported then the default file name of the output file is ligand pdbqt A report of the results and any errors that may have occurred appear at the bottom of the AutoDock Interface dialog box a Toclear the window click Clear Log Chapter 8 Docking 158 of 318 ChemBio3D 14 0 PerkinE For the Better a To save the log to file click Save Log a To change the folder in which the files are saved click Browse Work Folder Step 3 Optional Defining groups An atom group represents a binding site of interest that you define in the receptor cavity A group includes all atoms up to 10 you choose for the binding site and a radius in Angstroms that you define around the binding site F Note You do not have to define atom groups to perform docking calculations However if you do you must pre pare the receptor before you can define groups for it See Step 1 Preparing the receptor on page 157 When you perform docking AutoDock examines each ligand pose Afterward ChemBio3D determines whether any of the ligand atoms are within the radius of each group you define When you define a group you assign it as either an exclusion zone or an inclusion zone An exclusion zo
142. aw connection table file While ChemBio3D can read and assimilate any ChemBioDraw structure you can assist ChemBio3D in the two to three dimensional conversion of your models by following the suggestions in this chapter ChemBio3D uses the atom labels and bonds drawn in ChemDraw to form the structure of your model For every bond drawn in ChemDraw a corresponding bond is created in ChemBio3D Every atom label is converted into at least one atom Dative bonds are converted to single bonds with a positive formal charge added to one atom the atom at the tail of the dative bond and a negative formal charge added to the other the head of the dative bond Stereochemical relationships ChemBio3D uses the stereo bonds H Dot and H Dash atom labels in a ChemBioDraw structure to define the ste reochemical relationships in a model Wedged bonds in ChemBioDraw indicate a bond where the atom at the wide end of the bond is in front of the atom at the narrow end of the bond Wedged hashed bonds indicate the opposite the atom at the wide end of a wedged hashed bond is behind the atom at the other end of the bond As shown above the two phenyl rings are a trans formation about the cyclopentane ring The phenyl ring on the left is attached by a wedged hashed bond the phenyl ring on the right is attached by a wedged bond You can also use dashed hashed and bold bonds However be aware of potential ambiguity where these non directional bonds are used A
143. bility values reported are the first order alpha tensors xx yy ZZ XZ yZ Xy second order beta tensors and third order gamma tensors _ Note Polarizabilities cannot be calculated using the MINDO 3 potential function COSMO solvation in water The COSMO method is useful for determining the stability of various species in a solvent The default solvent is water For more information see the MOPAC online manual To run the COSMO method 1 Go to Calculations gt MOPAC Interface gt Compute Properties 2 On the Job amp Theory tab select COSMO in the Solvent field 3 On the Properties tab check the COSMO Area and or COSMO Volume properties f Note You can also use the Miertus Scirocco Tomasi solvation model which is available using the H2O keyword This method is recommended only for water as the solvent A discussion of this method can be found in the CS MOPAC online documentation Hyperfine Coupling Constants Hyperfine Coupling Constants are useful for simulating Electron Spin Resonance ESR spectra Hyperfine inter action of the unpaired electron with the central proton and other equivalent protons cause complex splitting patterns in ESR spectra ESR spectroscopy measures the absorption of microwave radiation by an unpaired electron when it is placed under a strong magnetic field Hyperfine Coupling Constants HFCs are related to the line spacing within the hyperfine pattern of an ESR spectra and the distance between pe
144. cally treated as spheres a Bonds are typically treated as springs a Non bonded interactions between atoms are described using potential functions derived from classical mechanics a ndividual potential functions are used to describe the different interactions bond stretching angle bending torsion bond twisting and through space non bonded interactions a Potential energy functions rely on empirically derived parameters force constants equilibrium values that describe the interactions between sets of atoms The sum of the interactions determines the conformation of the molecule a Molecular mechanical energies have no meaning as absolute quantities They can only be used to compare relative steric energy strain between two or more conformations of the same molecule The force field Since molecular mechanics treats bonds as springs the mathematics of spring deformation Hooke s Law is used to describe the ability of bonds to stretch bend and twist Non bonded atoms greater than two bonds apart interact through van der Waals attraction steric repulsion and electrostatic attraction and repulsion These properties are easi est to describe mathematically when atoms are considered as spheres of characteristic radii The total potential energy E of a molecule can be described by E Stretching energy Bending energy Torsion energy Non bonded interaction energy The first three terms the bonded interactions can be
145. cecececceeceeeeeeeeeeees 71 Stereo enhancement 0 222 eee ote ee en en es eee nk ede bee ee ete eee ete 71 Setting view fOCUS 20 eee cece cece ccc eee cece eee e cece cece eee cece eee c eee eeceeeeeeeeeeeeeeeeeees 72 Chapter 5 Building Advanced Models 020 0000 2 occ cece cece ccc ccc ccc cece aaan oaa anirno ranana 73 Dummy bonds and dummy atoms 2 222220 0 0 eee 73 MUDSUMICIUNES 2st cek i ae tee eens nate hase ated he ese eke etek 74 Bonding by proximity Acc 77 Setting measurements 2 2 e cece eee cece cece cee ce eee ceceeeeeeeeseeeeeeeeeeees 77 Atom and building types 2 000000 eee cece cece e ee ee cece cece eeeeeeeeeeeeeeeeecesseceeseeeees 80 Stereochemistry 2 e eee cece cece cece ce eee eee e eee ee cee ceeeeeeeeeeeeeeeees 84 Building with Cartesian tables 2 022 2 22 cece cece cece cece cece ce cece cece cece cece cece eect eeeeeeeeeeees 86 Table of Contents iii ChemBio3D 14 0 PerkinE For the Better Building models using ISIS Draw 0 02 2 2 c cece cece cece cece cece eee ecceeceececeeeeeees 87 kone electron pails 2p on shes e ge a e Na ee eal ie oe ea ae se et 87 Chapter 6 Computational Engines 2 000002 0 o oo c eee e cece cece cece cece eeeeeeeeeees 88 AD imito methods x22 2deo addenda Nc aa NU Stes cn data iets R d dap hap ded de anh Yt 88 Semi empirical methods _ 2 2 2 cece cece eee ccc e eee e cece cece eee e cece ILDA anaana nnana 88 Fo
146. chanics correction for amide bonds Use the additional keyword NOMM to turn this keyword off Electrostatic potential Use the electrostatic potential property when the element coverage of the AM1 potential function does not apply to the molecule of interest For more information see the MOPAC online manual This table contains the keywords sent to CS MOPAC and those you can use to affect this property Sent to CS MOPAC to specify the Electrostatic Potential routine POTWRT Add this keyword if you want to print out the ESP map values GEO OK Sent to CS MOPAC to override checking of the Z matrix MMOK Sent to CS MOPAC to specify Molecular Mechanics correction for amide bonds Use the additional keyword NOMM to turn this keyword off Molecular surfaces Molecular surfaces calculate the data to render the Total Charge Density Molecular Electrostatic Potential Spin Density and Molecular Orbitals surfaces Chapter 6 Computational Engines 118 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better Polarizability The polarizability and hyperpolarizability provides information about the distribution of electrons based on presence of an applied electric field In general molecules with more delocalized electrons have higher polarizability values Polarizability data is often used in other equations for optical properties of molecules For more information see the MOPAC online manual The polarizability and hyperpolariza
147. charge charge interactions Cutoff distance for charge dipole interactions a Cutoff distance for dipole dipole interactions Chapter 7 Parameter Tables 149 of 318 ChemBio3D 14 0 PerkinE For the Better Cutoff distance for van der Waals interactions MM2 atom type parameters The MM2 Atom Types table MM2 Atom Types xml contains the van der Waals parameters used to compute the force field for each atom in your model Each MM2 Atom Type record contains eight fields Atom type number R Eps Reduct Atomic Weight Lone Pairs Quality and Reference Text type number The Text number field is the atom type to which the rest of the MM2 Atom Type Parameter record applies The records in the MM2 Atom Type table window are sorted in ascending order of Atom Type Atom type number R The R field is the van der Waals radius of the particular atom The larger the van der Waals radius of an atom is the larger that atom 7 Note ChemBio3D uses the van der Waals radius R in the MM2 Atom Types table for computation It is not the same as the van der Waals radius in the Atom Types table which is used for displaying the model Eps The Eps or Epsilon field is a constant that is proportional to the depth of the potential well As the value of epsi lon increases the depth of the potential well increases as does the strength of the repulsive and attractive inter actions between an atom and other atoms f Note For specific van der Waals interac
148. ck OK Gibbs Free Energy Reported in KJ mole Gibbs free energy is defined as G p T U pV TS which is same as G p T H TS Where a U is the internal energy SI unit Joule a pis pressure SI unit Pascal a V is volume SI unit m3 a Tis the temperature SI unit Kelvin a Sis the entropy SI unit joule per Kelvin a His the enthalpy SI unit Joule 7 Note H and S are thermodynamic values found at standard temperature and pressure To calculate Gibbs free energy using either ChemPropPro or GAMESS 1 Go to Calculations gt Compute Properties 2 Expand either GAMESS Interface or ChemPropPro and select Gibbs Free Energy Chapter 11 Chemical properties 197 of 318 ChemBio3D 14 0 PerkinElmer For the Better 3 Click OK Harmonic Zero Point Energy In ordinary quantum mechanics the zero point energy is the energy associated with the ground state of the system One example is the energy associated with the ground state of the quantum harmonic oscillator expressed by h E w Where E is energy h is reduced Planck constant and is angular frequency To calculate frequencies using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Harmonic Zero Point Energy 3 Click OK Heat Capacity The amount of heat required to change a substances temperature by a given amount Values are measured in Cal Mol K To calculate heat capacity using Gaussian
149. ck the Build from Text tool 2 Click H10 type NO2 then press ENTER The para nitrophenoxide ion displays Perform minimization as in the last step For the last two monosubstituted nitro phenols first select the nitro group using the Select Tool and press DELETE Add the nitro group at the meta H9 or ortho H8 position and repeat the analysis The data from this series of analyses are shown below The substitution of a nitro group at para meta and ortho pos itions shows a decrease in negative charge at the phenoxy oxygen in the order meta gt para gt ortho where ortho sub stitution shows the greatest reduction of negative charge on the phenoxy oxygen You can reason from this data that the phenoxy ion is stabilized by nitro substitution at the ortho position Example 4 The polarizability of m Nitrotoluene Here is another example of calculating the dipole moment of a model Chapter 6 Computational Engines 123 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 This time we use m nitrotoluene 1 Go to File gt New 2 Click the Build from Text tool 3 Click in the model window A text box appears 4 Type m nitrotoluene and press ENTER A model of m nitrotoluene appears Reorient the model using the Rotate tool until it is oriented like the model shown below Figure 6 7 m nitrotoluene model 5 Go to Edit gt Select All 6 Go to View gt Model Display gt Show Serial Numbers Use CS MOPAC to find the dip
150. ctronegativity adjustments 00 0000000 o ccc ccc ccc cece cee cee ee cece eee eeeeeeeeeeeeeeeeeeeseeseeeees 147 IVI COPS CANS a eres se ed aaa nt lee SE 148 MM2 atom type parameters 2 2 2 0 22 22 o cece cece ccc ce ce cee eee cece cece eee A E Aa aa aa aaran aaan 150 Torsional parameters _ 22 2 222 222 c cece cece e cece cece eee eee cece cence cece eee ceeeeeeee cee eceeeeeeeeeeeeeeeeees 151 Out of plane bending 00000 eee eee aaa AoE E ELAI EDAD E a aaran aeann 153 van der Waals interactions 000000000a00aan0i0aniiianiennn ennor iann nann nn anona enaner arenan nren ar ennnen 153 Chapter 8 Docking 0 00000000000000 0000000000000000 0000da eaea Aaaa AAAA E E A Eao oroare arrena 155 Table of Contents iv ChemBio3D 14 0 PerkinE For the Better Installing AUtODOCK 2n 22c cece ce aces edeee betes eae ss dewdebeneliceiweeee te ie lowest a eree oroa Re nee ann 155 Installing AutoDock Tools 2 2 2 2 eee eee eee cece e cece cece cece eee cee cece eececeeceeceeeeeeeeeeeeees 155 Configuring AutoDock 0 0 22 2c ccc cece cece cece cece cece cece cece eee c cece eee e eee e eee eeteeeteeeeeeeees 156 Working with the AutoDock Interface 2 022 222 c cece cece cece aaran ainar rnanan 157 Step 1 Preparing the receptor 2 2 2 2 eee ccc cece cece cece ccc cece cece ccceececeeeceeeeeeeees 157 Step 2 Preparing the ligand 12 22 2222 ce cece cece cece cece cece cece cece teeeteeeetenees 158 Step 3 Optional
151. culation results file will be stored b Optional Select a directory in the Backup Calculations Files A backup file is stored in the location you select c Select Output files to display in notepad The files you select will appear in text files after the calculation is com plete a INI This file reports the options you selected in the Job amp Theory tab a BSO This file reports structural and thermodynamic properties of the model a FXO This file reports structural features of the model and data on the conformations that are found 5 Click Run MOPAC ChemBio3D supports CS MOPAC Ultra a molecular computation application that features several semi empirical methods 7 Note Before you install CS MOPAC you must install ChemBio3D With CS MOPAC you can Chapter 6 Computational Engines 110 of 318 ChemBio3D 14 0 PerkinElmer For the Better a Minimize Energy Optimizing geometry on page 112 a Optimizing to a Transition State Compute properties like Dipole moment Example 1 Dipole moment on page 121 a Cation stability Example 2 Cation stability on page 122 Charge distribution Example 3 Charge distribution on page 122 The polarizability of m Nitrotoluene Example 4 The polarizability of m Nitrotoluene on page 123 Phase stability Example 5 Phase stability on page 125 Hyperfine Coupling Constants Computing properties on page 115 UHF spin density Example 7 UHF spin d
152. d Cubic and Quartic Stretch Constants Integrating the Hooke s Law equation provides the Hooke s Law potential function which describes the potential energy of the ball and spring model The shape of this potential function is the classical potential well dV The Hooke s Law potential function is quadratic thus the potential well created is symmetrical The real shape of the potential well is asymmetric and is defined by the Morse Function but the Hooke s Law potential function works well for most molecules x x 1 2 V x dV k xdx kx f av if xdx Certain molecules contain long bonds which are not described well by Hooke s Law For this reason the MM2 force field contains a cubic stretch term The cubic stretch term allows for an asymmetric shape of the potential well thereby allowing these long bonds to be handled However the cubic stretch term is not sufficient to handle abnor mally long bonds Thus the MM2 force field contains a quartic stretch term to correct for problems caused by these abnormally long bonds Type 2 CHR Bending Force Parameters for C C C Angles CHR Bending K for 1 1 1 angles CHR Bending K for 1 1 1 angles in 4 membered rings CHR Bending K for 22 22 22 angles in 3 membered rings These constants are distinct from the force constants specified in the Angle Bending table The bending force con stant K for the 1 1 1 angle 1 is the atom type number for the C Alkane atom type listed in the
153. d and one maximum energy eclipsed conformation To minimize energy in ethane Optional Go to View gt Model Display gt Display Mode gt Ball amp Stick Build a model of ethane in an empty window Go to Calculations gt MM2 gt Minimize Energy 1 2 3 Optional Go to View gt Model Display gt Show Serial Numbers 4 5 Click Run The calculation results appear in the Output box The total steric energy for the conformation is 0 8180 kcal mol The 1 4 van der Waals term of 0 6756 dominates the steric energy This effect is caused by the H H repulsion contribution F Note The values of the energy terms shown are approximate and can vary slightly based on the type of processor used to calculate them To view the value of one of the dihedral angles that contributes to the 1 4 van der Waals contribution 1 Select the atoms making up the dihedral angle as shown in the figure below by SHIFT clicking H 7 C 2 C 1 and H 4 in that order Chapter 6 Computational Engines 96 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 9 rn 9 2 Go to Structure gt Measurements gt Display Dihedral Measurement Measurement Display Atorns Actual A Optimal A yy H06 C 1 C 2 445 60 1551 Figure 6 1 Dihedral measurement for ethane The displayed angle represents the lowest energy conformation for the ethane model Entering a value in the Optimal column imposes a constraint on the minimization rou
154. d CS GAMESS apply ab initio methods Semi empirical methods Semi empirical methods use approximations from experimental data to provide the input into the mathematical mod els The CS MOPAC and Gaussian computational engines use semi empirical methods Force field calculation methods A force field refers to the form and parameters of the calculations used to predict molecular properties For example you can use a force field calculation to predict the torsional constraint for a bond or the repulsion between molecules Force fields are used for a variety of calculations and are often verified with experimental values Chapter 6 Computational Engines 88 of 318 hemBio3D 14 I ChemBio3 0 PerkinE For the Better Compute properties Calculation of the energy of a molecule at a specific geometry is called single point energy computation Compute Properties represents a single point energy computation that reports the total steric energy for the current con formation of a model _ Note The Steric Energy is computed at the end of an MM2 Energy minimization A comparison of the steric energy of various conformations of a molecule gives you information on the relative sta bility of those conformations f Note If parameters are not available because the atom types in your model are not among the MM2 atom types supported ChemBio3D will approximate You can view the approximate parameters using the Show Used Para meters command after the a
155. d distances constraints keep that measurement constant or nearly so while the rest of the model is changed by the computation The constraint doesn t remove the atoms from a computation Chapter 5 Building Advanced Models 79 of 318 ChemBio3D 14 0 PerkinE For the Better Atom and building types Building types define the structure of your model the bond lengths bond angles and relative sizes of the atoms them selves By default ChemBio3D assigns building types as you build your model using a predefined set of building types However you can also create your own building types Where Building types define the structural aspects of a model atom types define attributes such as bond energies thermal properties and other nonstructural properties Force fields use the data to calculate properties of your model and predict model behavior Force field calculations take into account the type of each atom in your model the atom location and the functional group to which the atom belongs For example a carboxy carbon has a different atom type than an alkyl carbon For more information on how to add atom types to ChemBio3D see Modifying parameter tables on page 139 About Correct Atom Types Correct atom types determine whether atom types are assigned to each atom as you build Atom types such as C Alkane specify the valence bond lengths bond angles and geometry for the atom Building type characteristics The characteristics of an
156. d is not required in the calculation To perform an electrostatic calculation 1 Go to Calculations gt MMFF94 gt Perform MMFF94 minimization The Perform MMFF94 Minimization dialog box appears 2 Click the Electrostatic Calculations tab 3 Select a calculation method Set the value of the dielectric constant and the dielectric exponent for exact calculations The value of dielectric exponent can be 1 or 2 Set the value of Refinement and Expansion level for Fast Multipole Method calculations a Set the value of Order of Taylor expansion BMAX MAC Acceptance parameter and Maximum number of particles per node for Adaptive Tree Code calculations 4 Click Run The output window displays the calculation result Note When using either the FMM or ATC it is strongly recommended that you use one of the Van der Waals cutoff techniques or the Van der Waals terms will still scale as N2 time where N is the number of atoms Chapter 6 Computational Engines 93 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better van der Waals calculations van der Waals calculation is a non bonded energy calculation Attraction occurs at short range and rapidly decrease as the interacting atoms move apart even by a few angstroms Repulsion occur when the distance between inter acting atoms becomes even slightly less than the sum of their contact radii As the number of atoms increases van der Waals calculations may become time consuming ChemBio3D in
157. dashed hashed or bold bond must be between one atom that has at least three attachments and one atom that has no more than two attachments including the dashed hashed or bold bond Shown below the nitrogen atom is placed behind the ring system and the two methyl groups are placed in front of the ring system Each of these three atoms is bonded to only one other atom so they are presumed to be at the wide ends of the stereo bonds Chapter 13 2D to 3D Conversion 221 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 However in the next figure below the hashed bond is ambiguous because both atoms on the hashed bond are attached to more than two bonds In this case the hashed bond is treated like a solid bond Wavy bonds are always treated like solid bonds H Dots and H Dashes are also used to indicate stereochemistry H Dots become hydrogen atoms attached to carbon atoms by a wedged bond H Dashes become hydrogen atoms attached by a wedged hashed bond The following figure shows cis decalin on the left and trans decalin on the right as they would be drawn in ChemBioDraw to be read in by ChemBio3D Of course you can specify a cis fusion with two H Dots instead of two H Dashes Hittin nH H nH cis decalin trans decalin As a general rule the more stereo bonds you include in your model the greater is the probability that ChemBio3D will make correct choices for chirality and dihedral angles When converting t
158. del explorer isn t open already 2 Inthe model explorer right click the fragments that you want to add to the structure browser 3 Inthe context menu select Add to Structure Browser To remove fragments from the structure browser 1 Go to View gt Model Explorer if the model explorer isn t open already 2 Inthe model explorer right click the fragments that you want to remove from the structure browser 3 Inthe context menu select Remove from Structure Browser Making fragments exclusive in the structure browser Model explorer lets you make fragments exclusively available in the structure browser You can select one or more fragments in the model explorer and make it exclusive in the structure browser When you make a fragment exclusive in the structure browser only that item is available in the structure browser To make fragments exclusive in the structure browser Chapter 4 Displaying Models 57 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 1 Go to View gt Model Explorer if the model explorer isn t open already 2 Inthe model explorer right click the fragments that you want to make exclusive in the structure browser 3 Inthe context menu select Make exclusive in Structure Browser Measuring molecules You can display atomic distance bond angles and dihedral angles in the model window How to display individual measurements is described in this below For how to display all measurements in a model see T
159. dis playing the download instructions 3 Download and install AutoDock 4 2 3 to your local hard drive _ Note Ensure that you download AutoDock 4 2 3 and not AutoDock Vina 4 Inthe AutoDock dialog box click Set AutoDock Path to select the path to where you installed AutoDock Installing AutoDock Tools Like AutoDock the AutoDock tools are free to install However for the tools to function properly prior to installing them you must install Python 2 5 2 The installer for Python 2 5 2 is found at the following location http leg acy python org ftp python 2 5 2 python 2 5 2 msi Once Python is installed you can proceed with installing the AutoDock tools To install the AutoDock tools 1 In ChemBio3D go to Calculations gt AutoDock Interface gt Install AutoDock AutoDock Tools 2 Inthe AutoDock dialog box click Download AutoDock Tools The AutoDock Web site opens in a Web browser displaying the download instructions 1For more information see the AutoDock User Guide Chapter 8 Docking 155 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better 3 Download and install AutoDock Tools 1 5 4 to your local hard drive 7 Note You do not need to accept or install the packages listed at the end of the installation They are unnecessary for using the AutoDock tools 4 Inthe AutoDock dialog box click Set AutoDockTools Path to select the path to where you installed the AutoDock tools Configuring AutoDock When you dow
160. diting file format atom types on page 224 for instructions on modi fying or creating an atom type 12 Line 30 lt TRIPOS gt BOND is a Record Type Indicator RTI which begins a section containing information about the bonds associated with the molecule 13 Lines 31 49 each contain 4 fields describing information about a bond the first field is the bond id the second field is the from atom id the third field is the to atom id and the fourth field is the bond type FORTRAN formats The FORTRAN format for each record of the SYBYL MOL2 File format is as follows Molecule name file name H 5X Name 1X A Number of atoms number of bonds 4 1X 12 f 14 6X A2 3X 3F9 3 2X Atom type name coordinates and id A5 31 49 Bond id from atom to atom bond type 314 3X A2 Export file formats The following table shows all of the chemistry file formats that ChemBio3D supports Alchemy Alchemy Cartesian Cart Coords Coordinate 1 Cart Coords 2 Cambridge Crys tallographic Database Chapter 14 File Formats 255 of 318 ChemBio3D 14 0 Chem3D ae c3xml c3d Chem3D tem c3t plate Connection Table Conn Table CS GAMESS Input Gaussian Check point sma fam Gaussian fchk fch Gaussian Input Input Internal Coordin Int Coords Jint ates MacroModel MacroModel Maestro Maestro Molecular Design Limited MDL MolFile MolFile MSI MSI ChemNote m ChemNote MOPA
161. djacent bonds to select them Inthis case the middle atom s position remains fixed 2 Go to Calculations gt Dihedral Driver gt Double Angle Plot The Output window opens When the calculation is completed a graph displays theta 1 vs theta 2 Dihedral Driver Chart x Conformational Energy 180 2 85 Coo N 2 180 30 0 30 180 keaymol CBP C2 Cll HS idegrees 46 41 C 1 C 2 C 3 C 4X Gegrees lt Figure 17 15 The dihedral driver Chart A Legend bar 7 Note The chart is the result of rotating one angle through 360 in 10 increments while holding the other constant The second angle is then advanced 10 and the operation is repeated To view the conformation energy at any point click the point in the chart The model display rotates both dihedrals to the selected conformation energy Customizing the dihedral chart You can change how the chart colors and how the chart displays data Setting legend graph scale By default the chart displays data on a linear scale To change the scale from linear to logrithmic applies only to double dihedral charts 1 Right click anywhere on the chart 2 From the context menu select Set Legend Function 3 Select the desired log option The color map changes accordingly Hn computational chemistry energy minimization methods are used to compute the equilibrium configuration of molecules and solids Chapter 17 Tutorials 300 of 318 hemBio3D 14 I ChemBio3 0 Pe
162. ds O C N are rotatable where the atom on each end has at least one other non hydrogen sub stituent This topological parameter is a measure of molecular flexibility Unsaturated bonds and single bonds con nected to hydrogens or terminal atoms single bonds of amides sulphonamides and those connecting two hindered aromatic rings having at least three ortho substituents are considered non rotatable To calculate the number of rotatable bonds 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Num Rotatable Bonds 3 Click OK Ovality This refers to a measure of how the shape of a molecule approaches a sphere at one extreme or a cigar shape at the other Ovality is described by a ratio of volume to area O Al Axax 3xV l4xnyP Where A is area V is Volume and O is Ovality The ovality of a helium atom is 1 0 and HC 4H 12 triple bonds is 1 7 equivalent to 1 7 To report the ovality 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Ovality 3 Click OK The pKa describes the tendency of compounds or ions to dissociate in solution If B is defined as the conjugate base of the acid HB then pKa is calculated as pKa Log10 Ka where Ka H B HB To calculate pKa 1 Go to Calculations gt Compute Properties Chapter 11 Chemical properties 209 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 2 Expand Molecular
163. duce the problem before contacting us If you can reproduce the problem please record the exact steps Record the exact wording of any error messages that appear Record what you have tried to correct the problem Note The AutoDock and computation engines are third party products and may produce log files for the functions you run Refer to the log file to determine whether an issue you encounter is due to the third party product or ChemBio3D and provide this information when you contact technical support About ChemBio3D Tutorials There are twelve tutorials available from the Tutorials chapter They are broken into three categories and are situated throughout the Guide e Building Models e Tutorial 1 Building Models in 2D e Tutorial 2 Building with Bond Tools e Tutorial 3 Building Models with Text e Examining Models e Tutorial 4 Examining Conformations e Tutorial 5 The Dihedral Driver e Tutorial 6 Overlaying Models e Tutorial 7 Aligning Models e Tutorial 8 Viewing Orbitals Chapter 1 About ChemBio3D 3 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better e Tutorial 9 Mapping Surfaces e Tutorial 10 Partial Changes e Using Calculation Engines e Tutorial 11 Rotamer Analysis e Tutorial 12 Calculating Rotational Bonds These tutorials provide step by step instructions to help you work with the ChemBio3D tools From the Tutorials chapter you can quickly link to a specific tutorial situated elsewhere in anoth
164. e When coloring by partial charge atoms with a highly negative partial charge are deep blue Atoms with a highly pos itive partial charge are deep red As the partial charge gets closer to 0 the color becomes pale Atoms with a 0 partial charge are white The partial charge is the result of a calculation Extended Huckel CS MOPAC or Gaussian If you have not per formed a calculation the partial charge for each atom is 0 Figure 4 7 Color by partial charge Model Explorer The model explorer provides you with an easy way to explore the structure of any model even complex mac romolecules and alter display properties at any level The model explorer lists all the structures in the model window the atoms they contain and any structural features such as active sites in a protein that you may have defined To display the Model Explorer Go to View gt Model Explorer The display properties you can alter include a the display mode ball amp stick wire frame etc a visibility of each fragment a the color of the atoms in each fragment At the atom level you can display or hide a atom spheres a atom dots a element symbols a serial numbers Model Explorer also lets you add and remove fragments into Structure Browser window Chapter 4 Displaying Models 51 of 318 ChemBio3D 14 0 Perkin For the Better Model Explorer objects The model explorer displays all the objects in your model If your model consists of
165. e You can use the amino acid names preceded with a R to obtain the beta conformation for example HR Alak GlyR PheOH To generate the RB character type ALT 0223 using the number pad The appropriate bonding and dihedral angles for each amino acid are preconfigured in the substructure Chapter 5 Building Advanced Models 75 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 HAlaGlyPheOH polypeptide model Tip To view the alpha helix formation better use the Rotate Tool to reorient the model to an end on view To change the polypeptide to a zwitterion 1 Select the Build from Text tool 2 Click the terminal nitrogen A text box appears over the nitrogen atom 3 Type and press ENTER The charge is applied to the nitrogen atom Its atom type changes and a hydrogen atom is added 4 Click the terminal oxygen A text box appears over the oxygen atom 5 Type in the text box and press ENTER The charge is applied to the oxygen atom Its atom type changes and a hydrogen atom is removed Example 4 Other Polymers To build the model of a Polyethylene Terephthalate PET with four units type OH PET 4H into a text box with no atoms selected and press ENTER The H and OH are added to cap the ends of the polymer The PET model is shown below enn Figure 5 2 A PET polymer with four units Chapter 5 Building Advanced Models 76 of 318 ChemBio3D 14 0 PerkinE For the Better Bonding by proximity Atom
166. e keeping track of the section on which you are working becomes more difficult Using the View Focus feature you can set the focus on selected atoms so that you can pan to the atoms as desired To set the view focus 1 Select the fragment or set of atoms or bonds 2 Go to View gt View Focus gt Set Focus to Selection After you set the view focus if you continue building the model with the bond tools ChemBio3D will resize and repos ition the view so that all the atoms in the view focus are always visible As new atoms are added to the current model they become part of the view focus When rotating or resizing the view manually the rotation or resize will be centered around the view focus To set the view focus at the center of the Model window go to View gt View Position gt Center View on Focus To place the selected atoms of your model at the center of the Model window go to View gt View Position gt Center View on Selection Chapter 4 Displaying Models 72 of 318 ChemBio3D 14 0 I x PerkinElmer For the Better Building Advanced Models The advanced building features in ChemBio3D include options for enhancing your basic model structure defining your own building parameters and building models using data and structures from other sources Dummy bonds and dummy atoms A dummy bond lets you specify a connection between two atoms without a defined bond type Dummy bonds are often used in coordination complexes for inorganic comp
167. e Calculation To begin the computation click Run The computation begins Messages for each iter ation and any measurements you are tracking appear in the Output window The simulation ends when the number of steps specified is taken To stop the computation before it is finished click Stop in the Calculations toolbar Job type settings Use the Job Type tab to set options for the computation Select from these options Show Step Information Report each iteration in the Output box Copy Measurements to Output Box Track a particular measurement Move Only Selected Atoms Restrict movement of a selected part of a model during the minimization Save Step Data In Save a file containing the time in picoseconds total energy potential energy and temperature data for each step The word heating or cooling appears for each step in which heating or cooling was performed A summary of this data appears in the Message window each time a new frame is created The computation begins Messages for each iteration and measurements appear in the Output window The simulation ends when either the number of steps you specify is reached or you stop the computation Example Computing the Molecular Dynamics Trajectory for a Short Segment of Polytetrafluoroethylene PTFE To build the model 1 Go to File gt New 2 Select the Build from Text tool 3 Click in the model window A text box appears 4 Type F C2F4 6F and press ENTER A polyme
168. e MSI MolFile format file used by Chem3D Pro are discussed below Molecular Simulations MOLFILE ChemNote is a product of Molecular Simulations Inc Chapter 14 File Formats 239 of 318 ChemBio3D 14 0 Perkin For the Better The field value for Carbon 6 from the example file is included in parentheses for reference Line 1 is a standard header line for MSI MolFile format files Line 2 normally indicates the application which created the file Line 3 is the header for the File format version number section Line 4 indicates the file format version number The format for this field is YY MMDD Line 5 is the header for the File update version number section Line 6 indicates the file update version number The format for this field is YY MMDD Line 7 is the header for the molecule name section Line 8 contains the field molecule name This field contains either the file name or Undefined Name o AN Oa AON gt Line 9 is the header for the empirical formula 10 Line 10 contains the empirical formula field This field contains either the empirical formula or Undefined Empirical Formula 11 Lines 11 24 each contains information concerning conversions from 3D to 2D 12 Line 25 is the header for the Global display attributes section 13 Line 26 contains 5 fields describing the global display attributes Line thickness 1 font style 0 type face 1 type size 12 font 256 These values are specific to the platf
169. e Model Display tab 1 2 3 Select an option in the Model Type drop down list 4 Click Set as Default 5 Click OK The table below describes the display modes Chapter 4 Displaying Models 34 of 318 ChemBio3D 14 0 Wire Frame Sticks Space Filling Chapter 4 Displaying Models pP PerkinElmer For the Better Wire frame is the most simple display mode Bonds are displayed as pixel wide lines Atoms are not displayed explicitly but each half of a bond is colored to represent the element color for the atom Wire frame models are well suited for extremely large models such as proteins Stick models are similar to wire frame however the bonds are slightly thicker This model type is also good for visualizing very large models such as proteins These models show bonds as thick lines and atoms as filled spheres The atom spheres are filled with color that corresponds to the element or position of the atom These models are similar to Ball and Stick models except that all bond types are drawn as cylinders These models are best for getting an idea about the relative physical size of the atoms Each atom s size is determined by its van der Waal s VDW radius These models may be complex to draw and slow to display Atoms are scaled to 100 of the van der Waals radii specified in the Atom Types table The van der Waal s radii may be set so that overlap between non bonded atoms indicates a large about 0 5
170. e automatically added between pairs of atoms whose distance is less than that of the sum of the covalent radii of the two atoms The bond orders are guessed based on the ratio of the actual distance to the sum of the covalent radii The bond orders bond angles and the atom symbols are used to determine the atom types of the atoms in the model Chapter 14 File Formats 228 of 318 hemBio3D 14 I HnemBiog 9 PerkinElmer For the Better Triple Double Single Internal coordinates file Internal coordinates files INT Coords are text files that describe a single molecule by the internal coordinates used to position each atom The serial numbers are determined by the order of the atoms in the file The first atom has a serial number of 1 the second is number 2 etc The format for Internal coordinates files is as follows 1 Line 1 is a comment line ChemBio3D ignores this line Each subsequent line begins with the building type num ber 2 Line 2 contains the building type number of the Origin atom 3 Beginning with line 3 the building type number is followed by the serial number of the atom to which the new atom is bonded and the distance to that atom The origin atom is always the first distance defining atom in the file All dis tances are measured in Angstroms 4 Beginning with line 4 the distance is followed by the serial number of the first angle defining atom and the angle between the newly defined atom the distance defini
171. e fields in the Pi Atoms table are described below Atom Type The Atom type number field contains the atom type number to which the rest of the Conjugated Pisys tem Atoms record applies Electron The Electron field contains the number of electrons that the pi atom contributes to the pi system For example an alkene carbon atom type number 2 contributes 1 electron to the pi system whereas a pyrrole nitro gen atom type number 40 contributes 2 electrons to the pi system lonization The lonization field contains the amount of energy in electron volts eV required to remove a pi electron from an isolated pi atom The ionization energy increases as the electronegativity of the atom increases For example an alkene carbon has an ionization energy of 11 160 eV and the more electronegative pyrrole nitrogen has an ionization energy of 13 145 eV Repulsion The Repulsion field is a The energy required to keep two electrons each on separate pi atoms from moving apart The energy in electron volts eV required to keep two electrons occupying the same orbital on the same pi atom from moving apart The repulsion energy increases as the electronegativity of the atom increases For example an alkene carbon has an repulsion energy of 11 134 eV and the more electronegative pyrrole nitrogen has an repulsion energy of 17 210 eV The quality of a parameter indicates the relative accuracy of the data Accuracy Level The parameter is an est
172. e gt Minimize Energy 6 On the Job amp Theory tab choose PM3 7 On the Properties tab click Heat of Formation COSMO Area and COSMO Volume Chapter 6 Computational Engines 125 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 8 Click Run The results appear in the Messages window 9 Go to Calculations gt MOPAC Interface gt Minimize Energy 10 On the Property tab deselect COSMO Area and COSMO Volume 11 Click Run The results appear in the Messages window To create the zwitterion form 1 Click the Build from Text tool 2 Click the nitrogen atom type then press ENTER 3 Click the oxygen atom type then press ENTER The glycine zwitterion is formed Figure 6 9 Glycine zwitterion 4 Perform a minimization with and without the COSMO Area and COSMO Volume properties selected as per formed for the glycine model This table summarizes the results of the four analyses neutral H20 108 32861 52 36067 zwitterion H20 126 93974 52 37133 From this data you can reason that the glycine zwitterion is the more favored conformation in water and the neutral form is more favored in gas phase Example 6 Hyperfine Coupling Constants This is an example on Hyperfine Coupling Constants and it uses the ethyl radical To build the model Chapter 6 Computational Engines 126 of 318 hemBio3D 14 I ChemPlase LRG PerkinElmer For the Better Go to File gt New Model Click the Build fr
173. e initially assigned based on the order in which you add atoms to your model Chapter 4 Displaying Models 37 of 318 ChemBio3D 14 0 Perkin For the Better To reassign the serial number of an atom 1 Inthe model explorer select the atoms to renumber 2 Right click the selected atoms and go to Atom Serial Numbers gt Hide Atom Serial Numbers F Note The model explorer cannot update its numbering to match the changes you are making on the model when Serial Numbers are displayed If you forget this step you will see different numbers on the tree control and the model If this happens hide the serial numbers momentarily and display them again Click the Build from Text tool Click the atom you want to reserialize The atom is selected and a text box appears Type the serial number Press ENTER Right click the atom that you reserialized and go to Atom Serial Numbers gt Show Atom Serial Numbers The new serial number of the atom appears N DO oO Ff W 8 Repeat step 4 to step 7 for all the atoms that you want to reserialize If the serial numbers of any unselected atoms conflict with the new serial numbers then those unselected atoms are also reserialized To reserialize another atom with the next sequential number double click the next atom you want to reserialize To reserialize several atoms at once 1 Click the Build from Text tool 2 Hold down SHIFT and select several atoms 3 Type the starting serial numb
174. e of the run is the Step Interval times the number of steps Heating Cooling Rate dictates whether temperature adjustments are made If the Heating Cooling Rate check box is checked the Heating Cooling Rate slider determines the rate at which energy is added to or removed from the model when it is far from the target temperature To compute an isoenthalpic trajectory constant total energy deselect Heating Cooling Rate Target Temperature the final temperature to which the calculation will run Energy is added to or removed from the model when the computed temperature varies more than 3 from the target temperature The computed temperature used for this purpose is an exponentially weighted average temperature with a memory half life of about 20 steps 6 Click Run Saving a Job The job type and settings are saved in a JDF file if you click Save As on the dialog box before running a computation You can then run these computations in a later work session Starting the calculation To begin the computation click Run The computation begins Messages for each iteration and measurements you track appear in the Output window To stop the computation before it finishes click Stop in the Calculations toolbar Chapter 6 Computational Engines 101 of 318 ChemBio3D 14 0 PerkinElmer For the Better Molecular dynamics simulation using MM2 To perform a molecular dynamics simulation 1 Build the model or fragments _ Note The mod
175. e stretch bend force constants to lengthen the bonds from the central atom in the angle to the other two atoms in the angle For example the normal C C C bond angle in cyclobutane is 88 0 as compared to a C C C bond angle of 110 8 in cyclohexane The stretch bend force constants are used to lengthen the C C bonds in cyclobutane to 1 550A from a C C bond length of 1 536A in cyclohexane Sextic Bending Constant Sextic bending constant 10 8 ChemBio3D uses the sextic bending constant to increase the energy of angles with large deformations from their ideal value Dielectric Constants a Dielectric constant for charges Dielectric constant for dipoles The dielectric constants perform as inverse proportionality constants in the electrostatic energy terms The constants for the charge and dipole terms are supplied separately so that either can be partially or completely suppressed The charge dipole interaction uses the geometric mean of the charge and dipole dielectric constants For example when you increase the Dielectric constant for dipoles a decrease in the Dipole Dipole energy occurs This has the effect of reducing the contribution of dipole dipole interactions to the total steric energy of a molecule Electrostatic and van der Waals cutoff parameters These parameters define the minimum distance at which the fifth order polynomial switching function is used for the computation of the listed interactions a Cutoff distance for
176. ect Cv 3 Click OK Cluster Count The cluster count is the number of paths of a given length in the distance matrix To calculate the cluster count 1 Go to Calculations gt Compute Properties Chapter 11 Chemical properties 191 of 318 ChemBio3D 14 0 PerkinElmer For the Better 2 Expand Molecular Topology and select Cluster Count 3 Click OK Connolly Accessible Area This is the locus of the center of a spherical probe representing the solvent as it is rolled over the molecular model To report the Connolly accessible area 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Connolly Accessible Area 3 Click OK Note Connolly calculations are limited to molecules of 300 atoms or less Connolly Molecular Area This is the contact surface created when a spherical probe representing the solvent is rolled over the molecular model To report the Connolly molecular area 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Connolly Molecular Area 3 Click OK f Note Connolly calculations are limited to molecules of 300 atoms or less Connolly Solvent Excluded Volume This is the volume of space bounded by the solvent accessible molecular surface To report the Connolly solvent excluded volume 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Connolly Solvent Excluded Volume 3 Click OK f Note Connolly calculations are limi
177. ect Lipinski Rule 3 Click OK L7 Note You can also calculate the reported values separately LogP Partition Coefficient The partition coefficient is a ratio of concentrations of un ionized compound between two solutions To measure the partition coefficient of ionizable solutes the pH of the aqueous phase is adjusted so that the predominant form of the Chapter 11 Chemical properties 201 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 compound is un ionized The logarithm of the ratio of the concentrations of the un ionized solute in the solvents is called LogP Normally one of the solvents chosen is water the second is hydrophobic such as octanol The formula to calculate logP is solute l log P log octane ad solute ionizedwate To calculate LogP 1 Go to Calculations gt Compute Properties 2 Expand Molecular Networks and select LogP 3 Click OK Alternative method 1 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select LogP 3 Click OK Alternative method 2 1 Go to Calculations gt Compute Properties 2 Expand ClogP Driver and select Partition Coefficient 3 Click OK LogS The logarithm of the solubility of a substance measured in mol liter To calculate LogS 1 Go to Calculations gt Compute Properties 2 Expand Molecular Networks and select LogS 3 Click OK Lowdin Charges Is calculated using the formula 1 2 1 2 de Zp LSP
178. ecular geometry to be found without crossing a conformational energy barrier a Property calculation Predicts certain physical and chemical properties such as charge dipole moment and heat of formation Computational methods can perform more specialized functions such as conformational searches and molecular dynamics simulations Geometry optimization Before performing calculations on your model you may want to optimize its geometry by determining its stable con formations You can find the stable conformations by performing energy minimization calculations These calculations determine the model s local and global energy minima Geometry optimizations are iterative and begin at some starting geometry as follows 1 You first perform a single point energy calculation on the starting geometry 2 you change the coordinates for some subset of atoms and perform another single point energy calculation to determine the energy of that new conformation The first or second derivative of the energy depending on the method with respect to the atomic coordinates determines how large and in what direction the next increment of geometry change should be 3 The change is made 4 Following the incremental change ChemBio3D again determines the energy and energy derivatives and the pro cess continues until convergence is achieved at which point the minimization process terminates The accuracy of the energy minimization calculations depends
179. ee e eee ceeeeeteeeeceereetereeeeeeees 12 Selecting a display mode _ 2 eee 12 Using bond tools 2 2225 225 2cve aise yy Ss fo es ee eles Osos eee on Sule Einnar 13 Using the ChemDraw panel 0c cece cece cece eee e cece cece Eao AA Ea EAEn ranar raran eann 15 Using other 2D drawing packages 2 222 220 eee 15 Building from text 220000222 c cece cece cece cece cee cece eee ee eee cece eee ee te eeeeeeteeteetereeeeeees 16 Adding fragments 0 02 02 o cece ccc ccc ccc cece cece ee ee cee e cece bee eeeeeeeeeeeeeeeeeeeceeceseesceeeceseeeeees 18 Selecting atoms and bonds 222 eee 18 Atom Charges 22 24 82 05 ceveccacel cee as Ge sceca cell We chs ode eaa e Bes dose gs nace c nde EEEa E e SATE 21 OBJECt POSIION erster Ses oes fost deh oee NN dat ons ee hha e ceed feces See EES soa eae ee 23 NUDSIUICUINGS 4 os Ps De ta ae Pee see ea oes te Sate ee ese es Ales ee eee 24 Refining models 0 00000 o cece cece eee cece cece eee cece cece cece cece csc eeeeeeaseeeeseececeeceeeeeeeeees 27 Copying and printing 2 2 02 2222 c cece eee cece cece ADELEA ADe aoa earar eanan 28 Finding structures online 2020 22 22 c ccc cece cece eee cece ee eee eee cee aa aa oaaao naonana 32 Chapter 4 Displaying Models 000 eee e cece ee ceeeeeceeeeeeeeeeees 34 Table of Contents ii ChemBio3D 14 0 PerkinE For the Better DIS Play MOJE S ripe 2e cee ates sete gee ee ee orn Reena tooo aed T 34
180. el display type you use affects the speed of the molecular dynamics computation Model display will decrease the speed in the following order Wire Frame lt Sticks lt Ball and Sticks lt Cylindrical Bonds lt Rib bons lt Space Fill and van der Waals dot surfaces lt Molecular Surfaces 2 Totrack a particular measurement during the simulation select the appropriate atoms and do one of the following Go to Structure gt Measurements gt Set Bond Angle Go to Structure gt Measurements gt Set Bond Length 3 Go to Calculations gt MM2 gt molecular Dynamics The Molecular Dynamics dialog box appears 4 Enter the appropriate values Step Interval determines the time between molecular dynamics steps The step interval must be less than 5 of the vibration period for the highest frequency normal mode 10 fs for a 3336 cm 1 H X stretching vibra tion Normally a step interval of 1 or 2 fs yields reasonable results Larger step intervals may cause the integration method to break down because higher order moments of the position are neglected in the Beeman algorithm Frame Interval determines the interval at which frames and statistics are collected A frame interval of 10 or 20 fs gives a fairly smooth sequence of frames and a frame interval of 100 fs or more can be used to obtain samples of con formational space over a longer computation Terminate After causes the molecular dynamics run to stop after the specified number of steps
181. eld for an element The Color dialog box appears 3 Select the color to use and click OK 4 Close and save the table f Note You must save the changes for the new colors to take effect Coloring by group You can assign different colors to groups substructures in the model To change a color associated with a group in the active model 1 Inthe model explorer right click on the group name and choose Color gt Select Color The Color dialog box appears 2 Select the color to use and click OK Coloring by substructures If the groups in your model are substructures defined in the Substructures table substructures xml you can assign standard colors to them To assign or change a color 1 Go to View gt Parameter Tables gt Substructures 2 For the substructure whose color you want to change double click its corresponding cell in the Color column The Color dialog box appears 3 Select a color and click OK 4 Close and save the Substructures table Once colors are assigned in the Substructures table you can use them to apply color by group 1 Go to File gt Model Settings 2 Select the Colors amp Fonts tab 3 Select Group in the Color by section Each atom in your model appears in the color specified for its group Chapter 4 Displaying Models 50 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 _ Note Color by Group is displayed only in ribbon and cartoon display modes Coloring by partial charg
182. elow Chapter 15 References 278 of 318 h Bio3D 14 I ChemBio3 0 PerkinElmer For the Better Important factors relevant to AM1 are a AM1 is similar to MNDO however there are changes in the core core repulsion terms and reparameterization a AM1 is a distinct improvement over MNDO in that the overall accuracy is considerably improved Specific improve ments are a The strength of the hydrogen bond in the water dimer is 5 5 kcal mol in accordance with experiment a Activation barriers for reaction are markedly better than those of MNDO a Hypervalent phosphorus compounds are considerably improved relative to MNDO a n general errors in AH obtained using AM1 are about 40 less than those given by MNDO a AM1 phosphorus has a spurious and very sharp potential barrier at 3 0 The effect of this is to distort otherwise symmetric geometries and to introduce spurious activation barriers A good example is given by P406 in which the nominally equivalent P P bonds are predicted by AM1 to differ by 0 4A This is by far the most severe lim itation of AM1 a Alkyl groups have a systematic error due to the heat of formation of the CH2 fragment being too negative by about 2 kcal mol a Nitro compounds although considerably improved are still systematically too positive in energy The peroxide bond is still systematically too short by about 0 17A PM3 applicability and limitations Parameterized Model revision 3 PM3 may be applied t
183. ement table appears dis playing the angle value 3 Click and edit the value in the Actual column 4 Press ENTER Setting dihedral angles To set a dihedral angle 1 Select four contiguous atoms that define the dihedral angle Ti Note The first atom you select will move when the bond rotates 2 Go to Structure gt Measurements gt Display Dihedral Measurement The Measurement table appears displaying the angle value 3 Click and edit the value in the Actual column 4 Press ENTER Setting close contact distances Atoms that do not share a bond are considered close contacts To set the distance between two close contact atoms 1 Select any two atoms that do not share a bond _ Note The atom you select last moves when you set the distance between the atoms you select 2 Go to Structure gt Measurements gt Display Distance Measurement The Measurement table appears displaying the distance between the two atoms 3 Click and edit the value in the Actual column 4 Press ENTER 7 Note You can also move atoms using the Move Objects tool The Measurement table will automatically updated to reflect their new positions Chapter 5 Building Advanced Models 78 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Atom movement When you change the value of a measurement the last atom you selected moves ChemBio3D repositions the atoms that are attached to the moving atom and excludes atoms that are attached to othe
184. en bonds and polar hydrogen atoms ChemBio3D recognizes these hydro gen bond donor and acceptor groups Hydrogen bond donors a N H a O H Hydrogen bond acceptors a Oxygen atoms with at least one available lone pair Nitrogen atoms with at least one available lone pair To display hydrogen bonds do one of the following a Goto View gt Model Display gt Show Hydrogen Bonds and choose either Show Intermolecular or Show All a Goto File gt Model Settings and select the Model Display tab From the Hydrogen Bonds drop down list select Show intermolecular or Show All Hydrogen bonds appear as dashed lines between the donor hydrogen and the acceptor atom Bonds with less than ideal geometry are displayed with a blue tint The color intensity increases as the bond becomes less ideal Chapter 4 Displaying Models 44 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Figure 4 5 Hydrogen bonds in MM2 optimized water There are separate controls for hydrogen atoms and lone pairs and you can choose to display only polar hydrogens those bonded to oxygen or nitrogen To display hydrogen atoms and lone pairs 1 Go to File gt Model Settings The Model Settings dialog box appears 2 Click the Model Display tab 3 Select Show All from the Hydrogen Atoms drop down list 4 Select Show from the Lone Pairs drop down list 5 Click OK By default Show Polar is selected when a macromolecular PDB or mmCIF file is loaded
185. ene The counterintuitive fact that the V1 field is negative can be understood by remembering that only the total energy can be compared to experimental results In fact the total energy of trans 2 butene is computed to be 1 423 kcal mole lower than the total energy of cis 2 butene This corresponds closely with experimental results The negative V1 term has been introduced to compensate for an overestimation of the energy difference based solely on van der Waals repulsion between the methyl groups and hydrogens on opposite ends of the double bond This example illustrates an important lesson There is not necessarily any correspondence between the value of a particular parameter used in MM2 calculations and value of a particular physical property of a molecule V3 The V3 or 120 Periodicity Torsional constant field contains the third of three principal torsional constants used to compute the total torsional energy in a molecule V3 derives its name from the fact that a torsional constant of 120 periodicity can have three torsional energy minima and three torsional energy maxima within a 360 period A positive value of V3 indicates there are minima at 60 60 and 180 and there are maxima at 120 0 and 120 in a 360 period A negative value of V3 causes the position of the maxima and minima to be reversed as in the case of V1 and V2 above The significance of V3 is explained in the following example The 1 1 1 1 torsional paramet
186. ensity on page 128 RHF spindensity Example 8 RHF spin density on page 129 a Use CS MOPAC Properties a Use CS MOPAC files The procedures assume you have a basic understanding of the computational concepts and terminology of semi empirical methods and the concepts involved in geometry optimization minimization and fixed point computations Minimizing energy Minimizing energy is generally the first molecular computation performed on a model Go to Calculations gt MOPAC Interface gt Minimize Energy The CS MOPAC Interface dialog box appears with Minimize as a default Job Type Job Type Sets defaults for different types of computations Method Selects a method Wave Function Selects close or open shell See Specifying electronic configuration on page 272 for more details Optimizer Selects a geometry minimizer See Optimizing geometry on page 112 for more information Solvent Selects a solvent For more information on solvent effects see the online MOPAC manual Move Which lets you minimize part of a model by selecting it Minimum RMS Specifies the convergence criteria for the gradient of the potential energy surface See also Gradi ent norm on page 116 Coord System Specifies the coordinate system used for computation Use keyword 1SCF Specifies to do one SCF and then stop Use keyword MMOK GEO OK Specify Molecular Mechanics correction for amide bonds and also override some safety checks Notes RMS
187. eptor 1 Go to Calculations gt AutoDock Interface gt Setup AutoDock Calculation The AutoDock Interface dialog box opens Tip While using AutoDock you may want to ensure that the AutoDock Interface dialog box is always visible To ensure that dialog box stays visible right click the dialog box title bar and select Always on Top 2 Select the Prepare Receptor tab 3 To load a receptor do one of the following a Click Browse to load a receptor into AutoDock from a file a Click Import to load a receptor that is currently open as a model in ChemBio3D f Note The model must be in the active ChemBio3D window before you can import it Chapter 8 Docking 157 of 318 hemBio3D 14 I ChemBio3 0 PerkinE For the Better 4 Optional To prevent AutoDock from assigning new charges to the receptor select Preserve all input charges 5 To compute the receptor charges and determine atom types click Run After determining the charges and atom types AutoDock saves the results in the AutoDock work folder F Note The file is saved in the AutoDock work folder in pdbqt file format and the default file name will be of the format lt InputFileName gt _adv pdbqt For example if receptor pdb is the input file that you have imported then the default file name of the output file is receptor_adv pdbat A report of the results and any errors that may have occurred appear at the bottom of the AutoDock Interface dialog box To set t
188. er 4 Press ENTER Normally the selected atoms are reserialized in the order of their current serial numbers However the first four atoms selected are reserialized in the order you selected them Displaying atoms Using the model explorer you can control which atoms are displayed in the Model Window To hide atoms or groups right click at any level point to Visibility and click Hide Atom Group etc Hidden atoms or groups are displayed in parentheses in the tree control By default all levels in the hierarchy are set to inherit the settings of the level above but you can reset the default to hide a group but show individual atoms in it Showing atoms To show an atom in a hidden group right click the atom in the model explorer point to Visibility and click Show Chapter 4 Displaying Models 38 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Showing all atoms If you are working with a large model it may be difficult to keep track of everything you have hidden To show all atoms or groups that are hidden 1 Select a level in the tree control above the hidden atoms or groups or SHIFT click to select the entire model 2 From the context menu point to Select and click Select All Children 3 Right click again point to Show and choose Inherit Setting Atom symbols You can display symbols on the atoms in your model to explicitly show the elements they represent Figure 4 2 Glutamic acid with atom symbo
189. er a Increase the Virtual Memory VM Virtual memory extends RAM by allowing space on your hard disk to be used as RAM However the time for swapping between the application and the hard disk is slower than swapping with physical RAM Applications and Drivers As with most complex software applications there may be unusual circumstances in which ChemBio3D may become unresponsive Below are some recommended steps for you to follow to try to resolve software and driver issues 1 Restart Windows and try to reproduce the problem If the problem recurs continue with the following steps 2 The most common conflicts concem video drivers printer drivers screen savers and virus protection If you do need to contact us be sure to determine what type and version of drivers you are using a Video Driver related problems If you have problems displaying any ChemBioOffice Desktop Application try switching to the VGA video driver in the display Control Panel or System Setup and then retest the problems If using a different driver helps your original driver may need to be updated contact the maker of the driver and obtain the most up to date driver If you still have trouble contact us with the relevant details about the original driver and the resulting problem a Printer Driver related problems Try using a different printer driver If using a different driver helps your original driver may need to be updated contact the maker of the drive
190. er blank line 4 Line 4 the Counts line contains 5 fields which describes the molecule The first field is the number of atoms the second field is the number of bonds the third field is the number of atom lists the fourth field is an unused field and the fifth field is the stereochemistry F Note Chem3D Pro ignores the following fields number of atom lists the unused field and stereochemistry These fields will always contain a zero if the file was created using Chem3D Pro 5 Lines 5 23 the Atom block each contain 9 fields which describes an atom in the molecule The first field is the X coordinate the second field is the Y coordinate the third field is the Z coordinate the fourth field is the atomic sym bol the fifth field is the mass difference the sixth field is the charge the seventh field is the stereo parity des ignator the eighth field is the number of hydrogens and the ninth field is the center Note Chem3D Pro ignores the following fields mass difference charge stereo parity designator number of hydrogens and center These fields contain zeros if the file was created using Chem3D Pro 6 Lines 24 42 the Bond block each contain 6 fields which describe a bond in the molecule the first field is the from atom id the second field is the to atom id the third field is the bond type the fourth field is the bond stereo des ignator the fifth field is an unused field and the sixth field is the topology code 7
191. er chapter Chapter 1 About ChemBio3D 4 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 ChemBio3D Basics For the basic information about ChemBio3D functionality and use please follow the links below Getting around Learn and become familiar with the screen layout and its components Basic Model Building Learn to build your first model Tutorials Follow demonstrations on how to perform tasks in ChemBio3D Computational Engines Learn what computation methods are available in ChemBio3D Getting around This section describes the Graphic User Interface GUI with its various screen elements and its use S ChemBio30O Lra Untitied 1 canl Zax File Edit View Structure Calculations Surfaces Online Window Help B ay a Sa ae ae i a ee eee Te A BK Os Bm SBN BN 0 IP C1 es OO 3 Be RRAD SisFVAWNIALO Bi de tre C 2 a 2 e 8 MB iG Z Untitied 1L Gxmi b x ChemBioDraw Livelink gt a x QP QY Oe Chem smies Output E R fa E output B comments The main screen A Model window B Main menu C Toolbars D ChemDraw panel tab E Structure Browser tab F Model Explorer tab G Status bar H Output window Model window The work space where you build and view models Main menu Includes all tools necessary for building and viewing models running calculations and displaying chem ical properties Many of the menu options are also available in context menus Toolbars Cont
192. er does not attempt to completely describe the MM2 force field but discusses how the MM2 force field is used in ChemBio3D and the differences between this imple mentation Allinger s MM2 program QCPE 395 and Ponder s TINKER system M J Dudek and J W Ponder J Comput Chem 16 791 816 1995 For a review of MM2 and applications of molecular mechanics methods in general see Molecular Mechanics by U Burkert and N L Allinger ACS Washington D C USA 1982 Computational Chemistry by T Clark Wiley N Y USA 1985 also contains an excellent description of molecular mechanics For a description of the TINKER system and the detailed rationale for Ponder s additions to the MM2 force field visit the TINKER home page For a description and review of molecular dynamics see Dynamics of Proteins and Nucleic Acids J Andrew McCam mon and Stephen Harvey Cambridge University Press Cambridge UK 1987 Despite its focus on biopolymers this book contains a cogent description of molecular dynamics and related methods as well as information applicable to other molecules Allinger s force field The ChemBio3D implementation of the Allinger Force Field differs in these areas a Acharge dipole interaction term a A quartic stretching term a Cutoffs for electrostatic and van der Waals terms with a fifth order polynomial switching function Chapter 15 References 266 of 318 ChemBio3D 14 0 Perkin For the Better Automatic pi syste
193. er of HBond Acceptors Number of HBond Donors Num Rotatable Bonds o Ovality P LogP Partition Coefficient pKa Polar Surface Area Polarizability Potential Energy Principal Moment R Radius RMS Force Num Rotatable Bonds S SCF Energy Shape Attribute Shape Coefficient Spin Density Sum Of Degrees Sum of Valence Degrees T Thermodynamic Energy Topological Diameter Total Connectivity Total Energy Total Valence Connectivity vV Vapor Pressure WwW Water Solubility Wiener Index Z Zero Point Energy For more information on the Molecular Networks properties see Additional computational engines on page 1 Chapter 11 Chemical properties 189 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Balaban Index The Balaban index represented as J is defined as J E e edgesij Where a qis the number of edges in the molecular graph a u q n 1 is the cyclomatic number of molecular graph a nis the number of atoms in the molecular graph 4 S is the sum of all entries in the it row or column of the topological distance matrix of the molecule The distance matrix stores the shortest path between all pairs of atoms To calculate the Balaban index 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Balaban Index 3 Click OK Boiling Point The boiling point is report in Kelvin A solution boils at a slightly higher temperature than the pure so
194. er of n butane is an example of the V3 torsional constant The values of V1 V2 and V3 in the Torsional Parameters table are 0 200 0 270 and 0 093 respectively Because a positive value of V3 indicates that there are minima at 60 60 and 180 and there are maxima at 120 0 and 120 the minima at 60 signify the two conformations of n butane in which the methyl groups are gauche to one another The 180 minimum represents the conformation in which the methyl groups are anti to one another The maximum at 0 represents the conformation in which the methyl groups are eclipsed The maxima at 120 conform n butane in which a methyl group and a hydro gen are eclipsed The V1 and V2 torsional constants in this example affect the torsional energy in a similar way to the V1 torsional con stant for torsions about a carbon carbon double bond see previous example F Note The results of MM2 calculations on hydrocarbons do not correspond well with the experimental data on hydrocarbons when only the V3 torsional constant is used when V1 and V2 are set to zero However including small values for the V1 and V2 torsional constants in the MM2 calculations for hydrocarbons dramatically improve Chapter 7 Parameter Tables 152 of 318 ChemBio3D 14 0 Perkin For the Better F the correspondence of the MM2 results with experimental results This use of V1 and V2 provides little cor respondence to any particular physical property of hydrocarb
195. ero point energy for a conformation run a force operation using the keyword FORCE The zero point energy is found at the bottom of the out file The heat of formation in CS MOPAC is the gas phase heat of formation at 298K of one mole of a compound from its elements in their standard state The heat of formation comprises these terms AH Estee Bruel Eso tE atom where a E lec is calculated from the SCF calculation a E hu is the core core repulsion based on the nuclei in the molecule cl a E Sol and E tome are parameters supplied by the potential function for the elements within your molecule F Note You can use the keyword ENPART and open the out file at the end of a run to view the energy com ponents making up the heat of formation and SCF calculations See the MOPAC online manual reference for more information Gradient norm This is the value of the scalar of the vector of derivatives with respect to the geometric variables flagged for optim ization This property called GNORM in the MOPAC manual is automatically selected for a minimization which calculates the GNORM and compares it to the selected minimum gradient When the selected minimum is reached the minimization terminates Selecting this property fora Compute Properties operation where a minimization is not being performed will give you an idea of how close to optimum geometry the model is for the particular calculation Chapter 6 Computational Engine
196. ertia X Y Z Polar Surface Area R Radius S Shape attribute Shape coefficient Sum of degrees Sum of valence degrees T Total connectivity Topological diameter Topological index Total valence connectivity vV Vapor Pressure WwW Water Solubility Wiener Index 217 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Keyboard modifiers The following tables list the keyboard modifiers that let you manipulate your view of the model without changing tools Rotation Select the Rotate tool and Select the Rotate tool and rotate the selected object rotate all objects s At least one object must be selected SHIFT B Rotate 1 2 of fragment around bond SHIFT N which fragment rotates depends on the order in which the atoms were selected Rotate all objects at least Rotate model about the axis The model that includes one bond must be selected the selected bond rotates around the bond Rotate all objects about X Rotate model about the X axis axis Rotate all objects about Y Rotate model about the Y axis axis Rotate all objects about Z Rotate model about the Z axis axis In addition to the keyboard shortcuts you can rotate a model by dragging with the mouse while holding down both the middle mouse button or scroll wheel and the left mouse button Tip The order is important press the middle button first Chapter 12 Keyboard modifiers 218 of 318 pP PerkinElmer For the Be
197. erties 2 Select Electron Density and click Run The results appear in the Atom Property window To calculate the electron density using Gaussian 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select Electron Density 3 Click OK Another alternative method 1 Go to Calculations gt Gaussian Interface gt Compute Properties 2 Inthe Gaussian Interface dialog box select the Jobs tab and then select the Properties tab 3 Inthe Properties tab select the Electron Density checkbox 4 Click Run The results appear in the Atom Property window Electrostatic Potential The formula for electrostatic potential V at a point F fora system of charges q is at points r in a medium of dielec tric constant is expressed as Chapter 11 Chemical properties 194 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 q y Dar F You can calculate the electrostatic potential using GAMESS To calculate the electrostatic potential 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Electrostatic Potential 3 Click OK An alternative method 1 Go to Calculations gt GAMESS Interface gt C ompute Properties 2 Inthe Properties tab select Electrostatic Potential and click Run Elemental Analysis This is a process in which a material is analyzed for its elemental and isotopic composition Elemental analysis can be qualitative determining what element
198. erties of specific geometry of a model The values of these properties depend on where the model lies on the potential surface as follows Asingle point energy calculation at a global minimum provides information about the model in its most stable con formation a A single point calculation at a local minimum provides information about the model in one of many stable con formations A single point calculation at a saddle point provides information about the transition state of the model Chapter 9 Computation Concepts 170 of 318 ChemBio3D 14 0 PerkinElmer For the Better a A single point energy calculation at any other point on the potential energy surface provides information about that particular geometry not a stable conformation or transition state Single point energy calculations can be performed before or after optimizing geometry f Note Do not compare values from different methods Different methods rely on different assumptions about a given molecule and the energies differ by an arbitrary offset Molecular mechanics theory in brief Molecular mechanics computes the energy of a molecule in terms of a set of classical potential energy functions The potential energy functions and the parameters used for their evaluation are known as a force field Molecular mechanical methods are based on several principles a Nuclei and electrons are lumped together and treated as unified particles atoms a Atoms are typi
199. es tab select Charges in the Properties list 4 Select Wang Ford from the Charges list 5 Click Run The results for the model appear in the Message window when the computation is complete The molecules are now planar reflecting sp2 hybridization of the central carbon From these simple computations you can reason that the charge of the cation is not localized to the central carbon but is rather distributed to different extents by MMOK sent to CS MOPAC to specify Molecular Mechanics correction for amide bonds Use the additional keyword NOMM to tum this keyword off Example 3 Charge distribution In this example we analyze the charge distribution in a series of mono substituted phenoxy ions 1 Go to File gt New Model 2 Click the Build from Text tool 3 Click in the model window 4 Type PhO and press ENTER A phenoxide ion model appears F Note All the monosubstituted phenols under examination are even electron closed shell systems and are assumed to have Singlet ground state No modifications by additional keywords are necessary The default RHF computation is used 5 Go to Calculations gt MOPAC Interface gt Minimize Energy 6 On the Theory tab choose PM3 This automatically selects Mulliken from the Charges list 7 On the Property tab select Charges Chapter 6 Computational Engines 122 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better 8 Click Run To build the para nitrophenoxide ion 1 Cli
200. ethane This staggered conformation where the hydrogen atoms on adjoining carbons are a maximum distance from one another represents the most stable conformation of ethane The global minimum in the potential energy plot rep resents this conformation Chapter 17 Tutorials 296 of 318 ChemBio3D 14 0 PerkinElmer For the Better To calculate the steric energy of this conformation 1 Go to Calculations gt MM2 gt Compute Properties The Compute Properties dialog box appears 2 Inthe Properties tab select Pi Bond Orders and Steric Energy Summary Tip Use SHIFT click to select the properties 3 Click Run The Output box appears beneath the model window with steric energy results displayed The last line displays the total energy Output tmz Calculation completed successfully Note All parameters used are finalized Quality 4 Stretch 0 0000 Bend 0 0005 Stretch Bend 0 0000 Torsion 0 0000 Non 1 4 VDU 0 0000 1 4 VDW 0 9761 Total Energy 0 9766 kcal mol The total energy for this frame 0 977 kcal mol Calculation ended _ Note The values of the energy terms can vary depending on your computer processor To obtain the eclipsed conformation of ethane you rotate a dihedral angle torsional angle This is a common way to analyze the conformational space for a model To view dihedral angles 1 Go to Structure gt Measurements gt Generate All Dihedral Angles All of the model s dihedra
201. eton of a model in the ChemDraw panel or with the bond tools then change some of the carbons into other elements using the Build from Text tool After building a basic model you may wish to explore some of the basic ChemBio3D features For example you can move hide and resize objects For better viewing you can also rotate move and scale your model Default settings If you are new to ChemBio3D we recommend that you choose the default settings and an appropriate display mode It is suggested to choose Ribbon or Cartoons display mode for protein molecules and Wire Frame or Ball and Stick dis play mode for large molecules You may choose any display mode for small molecules as they render well in any dis play mode The appearance of the models depends on the selected display mode To apply the default settings 1 Go to File gt Model Settings The Model Settings dialog box appears 2 Click Reset to Default 3 Click OK Selecting a display mode Choosing the cylindrical bonds display mode ensures that your models look similar to what you see in this guide To select the display mode do one of the following Goto View gt Model Display gt Display Mode gt Cylindrical Bonds On the Model Display toolbar click the drop down arrow next to and select Cylindrical Bonds from the drop down list f Note To activate the Model Display toolbar go to View gt Toolbars gt Model Display For more information see Display modes
202. exist for organic compounds In this case ChemBio3D makes an educated guess wherever possible A message indicating an error in your model may appear before you start the analysis If you ignore the error you can determine the parameters guessed after the analysis To view the parameters used in an MM2 analysis go to Calculations gt MM2 gt Show Used Parameters Estimated parameters have a quality value of 1 Modifying parameter tables 7 Note Adding or changing parameters is not recommended unless you are sure of the information your are adding such as new parameter information documented in journals To add a new parameter to a parameter table 1 Goto View gt Parameter Tables and choose the parameter table to open 2 Do one of the following a Inthe table right click a row header and choose Append Row from the context menu A blank row is added to the bottom of the list Click a row header to select the row right click in the selected row and choose Insert Row A blank row is added above the row you selected 3 Type the information for the new parameter 4 Close and save the file _ Note Do not duplicate rows in a parameter table Duplicate parameters to be used in calculations cannot be determined Chapter 7 Parameter Tables 139 of 318 ChemBio3D 14 0 PerkinE ag For the Better amp Caution The parameter tables are designed to be edited However it is strongly recommended that you do not edit the tables u
203. experimental data or data from ab initio for parameters Requires experimental data or data from ab initio for parameters Less rigorous than ab initio methods Computationally intensive pP PerkinElmer For the Better Large systems thousands of atoms Systems or processes with no breaking or forming of bonds Medium sized systems hun dreds of atoms Systems involving electronic transitions Small systems tens of atoms Systems involving electronic transitions Molecules or systems without available exper imental data new chemistry Systems requiring rigorous accuracy 169 of 318 ChemBio3D 14 0 Perkin For the Better Potential energy surfaces A potential energy surface PES can describe A molecule or ensemble of molecules having constant atom composition ethane for example ora system where a chemical reaction occurs Relative energies for conformations eclipsed and staggered forms of ethane Potential energy surfaces can differentiate between Molecules having slightly different atomic composition ethane and chloroethane a Molecules with identical atomic composition but different bonding patterns such as propylene and cyclopropane Excited states and ground states of the same molecule The true representation of a model s potential energy surface is a multi dimensional surface whose dimensionality increases with the number of atom coordinates Since each
204. f 318 ChemBio3D 14 0 PerkinE For the Better 6 Lines 24 42 of the CT Block each contains 3 fields describing a bond between the two atoms The first field is the serial number of the atom from which the bond starts the second field is the serial number of atom where the bond ends and the third field is the bond order 7 Line 43 starts the block named CO The information in this block includes the Cartesian coordinates of all the atoms from the CT block and indicates the type of coordinates used Angstroms in this example Also in this line is the number of lines in the block 20 in this example 8 Line 44 contains two fields The first field contains the exponent used to convert the coordinates in the lines fol lowing to the coordinate type specified in line 43 The second field is the FORTRAN format of the atom coordin ates 9 Lines 45 65 each contains three fields describing the Cartesian coordinates of an atom indicated in the CT block The first field is the X coordinate the second field is the Y coordinate and the third field is the Z coordinate SYBYL MOL file The SYBYL MOL File format SYBYL is defined in Chapter 9 SYBYL File Formats pages 9 1 through 9 5 of the 1989 SYBYL Programming Manual The table below is an example of a file in SYBYL format produced in ChemBio3D This file describes a model of cyc lohexanol 19 MOL Cyclohexanol0 1 068 0 3581 0 0 207 1 2238 0 1 473 0 3737 0 1 1286
205. f groups This becomes useful when you want to highlight dif ferent parts of your model or assign attributes To move an object click drag it from one group or another To move several objects first select them using either CTRL click or SHIFT click Nesting objects You can also put objects in other objects For example you can have a DNA fragment that contains two helix groups that in turn contains nucleic acid groups There are a few things to keep in mind when you move objects Chapter 4 Displaying Models 56 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 a You cannot click drag objects from one fragment to another For example you cannot move atoms from one molecule to another a You cannot rearrange atoms within a group Display modes for fragments Using the model explorer you can change the display mode for one or more fragments 1 Inthe model explorer select the fragment s 2 Right click in the model explorer window 3 Go to Display Mode and select a display mode option For more information see Display modes on page 34 Figure 4 9 Cartoon left and ribbon right display modes in the model explorer Structure browser adding and removing fragments You can add or remove fragments from the model explorer into the structure browser The fragments you add to the structure browser appear in the model window To add fragments into structure browser 1 Go to View gt Model Explorer if the mo
206. file Advanced mode If you are an expert user you can go directly to a text entry window similar to the input template Go to Calculations gt Gaussian Interface gt Use Advanced Mode Click Online Gaussian 2003 Keywords to open the keywords page of the Gaussian Web site Optimize to transition state To optimize your model to a transition state use a conformation that is as close to the transition state as possible Do not use a local or global minimum because the algorithm cannot move the geometry from that starting point To optimize a transition state 1 Go to Calculations gt Gaussian Interface gt Optimize to Transition State The Gaussian Interface dialog box appears with Optimize to Transition State as the default Job Type 2 Youcan use the defaults or set your own parameters _ Note Unless you are an experienced Gaussian user use the Transition State defaults 3 On the Properties tab select the properties you wish to calculate from the final optimized conformation 4 On the General tab type any additional keywords that you want to use to modify the optimization 5 Click Run Minimizing energy Minimizing energy is generally the first molecular computation you will perform on a model You may minimize all or part of a model To minimize the part of a model first select the part to include or exclude from the minimization See Other Options on page 107 1 Go to Calculations gt Gaussian Interface gt Minimize Energy Geo
207. files between ChemBio3D and the ChemBio3D iPad app The Dropbox plug in can be downloaded from the Dropbox Web site Docking AutoDock helps you determine how one or more small molecules may be arranged to fit inside the cavity of a larger molecule You choose the molecules the cavity binding sites and calculation parameters AutoDock cal culates and displays the conformers and positions of each small molecule that fit your requirements For more information see Docking on page 155 Recent Additions viii pP PerkinElmer For the Better ChemBio3D 14 0 CONFLEX CONFLEX is a conformational analysis package developed by the CONFLEX Corporation Using CONFLEX you can search for low energy conformers of a model and create a fragment for each one in its optimal state For more information see C ONFLEX on page 109 Molecular Networks integration ChemBio3D incorporates new features from Molecular Networks for determining pKa LogS and LogP solubility properties See ChemBio3D properties on page 189 Also see About Molecular Net works on page 2 Recent Additions ix hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better About ChemBio3D ChemBio3D is part of the ChemBioOffice suite and lets you build visualize and analyze 3D models of chemical struc tures ChemBio3D models can be imported into desktop publishing tools or displayed on the Web ChemBio3D comes with GAMESS an ab initio quantum chemistry package GAMESS Let
208. force field such as metals The atom type numbers for these atom types range from 111 to 851 The atom type number for each of the non MM2 atom types in the MM2 Atom Type Parameters table is based on the atomic number of the element and the number of Chapter 6 Computational Engines 91 of 318 ChemBio3D 14 0 Perkin For the Better ligands in the geometry for that atom type To determine an atom type number the atomic number is multiplied by ten and the number of ligands is added For example Co Octahedral has an atomic number of 27 and six ligands There fore the atom type number is 276 In cases where different atom types of the same element have the same number of ligands the number nine is used for the second geometry Iridium Tetrahedral Atom Type 774 and Iridium Square Planar Atom Type 779 The rectification type of all the non MM2 atom types in the ChemBio3D Parameter tables is hydrogen H For more information on rectification types see Building types on page 140 Viewing MM2 parameters To view the parameters that ChemBio3D uses to perform MM2 computations go to View gt Parameter Tables gt MM2 Atom Type Parameters Editing MM2 parameters You can edit the parameters that come with ChemBio3D Parameters that you add or change can be guesses approx imations or values from literature In addition there are several adjustable parameters available in the MM2 Constants table 7 Note Before editing we recommend that
209. full products plugins and upgrades for the scientific community For molecular mod eling and other software visit the SciStore Web site and go to Software gt Chemistry gt Molecular Modeling in the SciStore main menu PerkinElmer Informatics Go to Online gt Browse CambridgeSoft com See the PerkinElmer Informatics Web site for the latest software databases services video tutorials and much more Online documentation Go to Online gt Browse CambridgeSoft Documentation Download and view documentation for all of our software products Online registration Go to Online gt Register Online Register your copy ChemBio3D and your other software ChemOffice SDK Go to Online gt Browse ChemOffice SDK Refer to the SDK for documentation sample code and other resources for the ChemOffice component APIs Troubleshooting This section describes steps you can take that affect the overall performance of CS Desktop Applications as well as steps to follow if your computer crashes when using a CS software product Performance Below are some ways you can optimize the performance of ChemBioOffice Desktop Applications Inthe Performance tab in the System control panel allocate more processor time to the application Install more physical RAM The more you have the less ChemBioOffice Desktop Applications will have to access your hard disk to use Virtual Memory Chapter 16 Online Resources 282 of 318 ChemBio3D 14 0 Perkin For the Bett
210. g the Run Gaussian Input file within ChemBio3D or using Gaussian directly Gaussian Checkpoint A Gaussian Checkpoint file FCHK FCH stores the results of Gaussian Calculations It contains the final geometry electronic structure including energy levels and other properties of the molecule Checkpoint files are supported for import only ChemBio3D displays atomic orbitals and energy levels stored in Checkpoint files If Cubegen is installed molecular surfaces are calculated from the Checkpoint file Gaussian Cube A Gaussian Cube file CUB results from running Cubegen on a Gaussian Checkpoint file It contains information related to grid data and model coordinates Gaussian Cube files are supported for import only ChemBio3D displays the surface the file describes If more than one surface is stored in the file only the first is dis played You can display additional surfaces using the Surfaces menu Internal Coordinates Internal Coordinates INT files are text files that describe a single molecule by the internal coordinates used to pos ition each atom The serial numbers are determined by the order of the atoms in the file The first atom has a serial number of 1 the second is number 2 and so on Internal Coordinates files may be both imported and exported You cannot use a Z matrix to position an atom in terms of a later positioned or higher serialized atom If you choose the second or third options in the Internal Coordinates Options
211. ge in the Pop up Information tab of the Model Settings dialog box then the partial charges will appear as part of the pop up information when you point to an atom Chapter 4 Displaying Models 66 of 318 ChemBio3D 14 0 PerkinElmer For the Better Solvent accessible surface The solvent accessible surface represents the portion of the molecule that solvent molecules can access To determine the solvent accessible surface a small probe sphere simulating the solvent molecule is rolled over the surface of the molecule van der Waals surface The solvent accessible surface is defined as the locus described by the center of the probe sphere as shown in the diagram below Q _ Figure 4 13 van der Waals surfaces A van Der Waals surface B Solvent Accessible surface C Solvent Probe Connolly molecular surface The Connolly surface also called the molecular surface or solvent exclusion surface is defined as the surface made by the center of a solvent sphere as it contacts the van der Waals surface The volume enclosed by the Connolly sur face is called the solvent excluded volume These surfaces are shown below Chapter 4 Displaying Models 67 of 318 hemBio3D 14 I enemBiog 9 PerkinElmer For the Better Figure 4 14 Connolly molecular surface A van Der Waals surface B Connolly surface C Solvent accessible Figure 4 15 Connolly surface of icrn Total charge density The total charge density is the electr
212. gments 1 For the first pair of atoms select the tertiary carbon on the benzene ring in the epinephrine fragment and in the methamphetamine fragment SHIFT click both atoms using the Select tool 2 Go to Structure gt Measurements gt Display Distance Measurement The Measurement table appears showing the distance between the two selected atoms 3 For the second pair of atoms in each structure select the carbon that is opposite the carbon atom you selected for the first pair of atoms 4 Go to Structure gt Measurements gt Display Distance Measurement 5 For the third pair of atoms select the nitrogen atom in each structure 6 Go to Structure gt Measurements gt Display Distance Measurement After you define the pairs of atoms you overlay one structure on the other by setting the distance measurement to zero for each pair of atoms and then perform the overlay calculation 7 Inthe Measurement table type 0 into the Optimal column for each atom pair and press ENTER Chapter 4 Displaying Models 61 of 318 ChemBio3D 14 0 I x PerkinElmer For the Better Actual A Optimal A 1 C 2 1 5230 0 0000 Figure 4 12 Adding optimal values to the Measurement table 8 Go to Structure gt Overlay gt Minimize The Overlay dialog box appears 9 Type 0 100 for the Minimum RMS Error and 0 010 for the Minimum RMS Gradient The overlay computation will stop when either the RMS Error becomes less than the Minimum RMS Error o
213. gn View X Y Plane With Selection The model moves to the position shown in Figure C A Applying color Although you can use color to add visual appeal to a model color can also be an important tool for identifying model fragments functional groups surfaces and individual atoms Customizing the background You can change the background color or replace the background with a picture such as your company logo A dark background is often suitable for ribbon displays intended for full color viewing whereas a light background is useful for print Chapter 4 Displaying Models 48 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 To customize the background 1 Go to File gt Model Settings and select the Background tab 2 Choose from these options a To change the background color select from the Background Color drop down list a To insert a picture select Background Picture and choose from the Transparency and Position options to modify the picture a To return to the default background click Reset to Default 3 Click OK _ Note The background colors are not saved in PostScript files or used when printing except when you use the rib bons display Coloring selected atoms To change the color of one or more atoms 1 Select the atom s 2 Right click an atom you selected and choose Color gt Select Color in the context menu The Color dialog box appears 3 Select a color and click OK The color of
214. graph 2 To see the conformation energy through a range of rotation angles click and drag across the chart while viewing the model Dihedral Driver Chart x Conformational Energy E B30 4 fi aa a aa a 4 1 0 7 YS a 100 1s ET a D 45 a 15 100 Figure 17 14 A dihedral driver single plot chart for ethane _ Note The dihedral rotates in 5 increments through 360 for a total of 72 conformations to produce the graph You can view the minimized energy values for each point in the Output window To rotate the other dihedral angle other end of the bond right click in the Dihedral Driver Chart and choose Rotate other End Recomputing with minimization Simple rotation does not take into account other conformational changes that may occur upon dihdral rotation e g angle bending As a result your model may depict high energy strain at various bonds or conformational strain between atoms As a result your model may not accurately represent the actual molecule and correspondingly the graph in the Dihedral Driver Chart dialog box may not be accurate To obtain an accurate graph consider recom puting with energy minimization Chapter 17 Tutorials 299 of 318 ChemBio3D 14 0 PerkinElmer For the Better To produce the graph with energy minimization right click on the Dihedral Driver Chart dialog box and select Recompute with Minimization Rotating two dihedrals To rotate two dihedrals 1 SHIFT click two a
215. h carbon atoms 2 Go to View gt View Position gt Align View Z Axis With Selection 7 Note If you perform an Energy Minimization from the same starting dihedral your model would optimize to the staggered conformation of ethane where the dihedral is 60 degrees instead of optimizing to the transition state Computing properties To perform a single point calculation on the current conformation of a model 1 Go to Calculations gt MOPAC Interface gt Compute Properties The Compute Properties dialog box appears Chapter 6 Computational Engines 115 of 318 ChemBio3D 14 0 PerkinElmer For the Better 2 Onthe Job amp Theory tab choose a potential energy function for performing the calculation 3 On the Properties tab a Select the properties b Select the charges c Set the value of Dielectric constant 4 On the General tab type any additional keywords if necessary 5 Click Run CS MOPAC properties This section describes the properties that you can calculate for a given conformation of your model either as a single point energy computation using the Compute Properties command or after a minimization using either the Minimize Energy or Optimize to Transition State commands Heat of formation AH This represents the heat of formation for a model s current conformation It is used for comparing the stability of con formations of the same model _ Note The heat of formation includes the zero point energies To obtain the z
216. h one from another This is where atom serial numbers and labels become useful 1 Go to View gt Model Display gt Show Serial Numbers or click the Serial Number icon on the Model Display tool bar 2 Go to View gt Model Display gt Show Atom Symbols or click the Atom Symbol icon on the Model Display toolbar _ Note The serial numbers that appear do not reflect a normal ordering because you started with a smaller model and built up from it If you want you can change the numbering order by choosing which atom is numbered first To renumber the atoms 1 Select the Build from Text tool AH 2 Click the first atom you want to number A text box appears on the atom C 1 C 2 Length 1 5235 Order 1 000 Figure 17 8 Adding atom symbols and numbers 3 Type the number you want to assign to this atom 1 for this example 4 Press ENTER The first atom is renumbered as 1 Chapter 17 Tutorials 291 of 318 ChemBio3D 14 0 Perkin For the Better 5 Double click each of the atoms in the order you want them to be numbered 6 Go to View gt Model Display gt Show Hydrogen atoms gt Show All and examine the model using the Rotate Tool Structure Cleanup As you build a model you may accidentally distort bond angles and bond lengths To correct for this 1 Go to Edit gt Select All All the atoms in the model are selected 2 Go to Structure gt Clean Up Saving the model Before moving to the next tutorial you may want to save a
217. hapter 3 Basic Model Building 26 of 318 ChemBio3D 14 0 Perkin For the Better Attachment points follow these rules a If two atoms in the substructure are the same the atom with the lowest serial number becomes the first attachment point a If anatom has an open valence and is attached to a selected atom it is numbered after any atom that is attached to an unselected atom a fanatomis attached only to rectified atoms it goes after any atom that is attached to non rectification atoms a If two atoms are the same according to the above criteria then the one attached to the atom with the lowest serial number goes first Refining models After building a 3D model you may need to make further refinements to help ensure that it is geometrically and struc turally correct For example bond angles and lengths may not be chemically accurate if you ve moved objects around or deleted them while building your model You may also need to rectify atoms in your model to adjust their valences in cases where you may have deleted other atoms Rectifying atoms When you rectify atoms in your model hydrogen atoms are added and deleted as necessary so that each selected atom is bonded to the correct number of atoms The correct number is specified by the valency of the atom type The rectify command assigns atom types before rectification The atom types of the selected atoms are changed so that they are consistent with the bound to orders and bound to
218. he AutoDock work folder go to the General tab and click Browse Work Folder a To clear the window click Clear Log a Tosave the log to file click Save Log A log file is saved in the working directory a Tochange the folder in which the files are saved or to open the log file click Browse Work Folder j Caution Do not close the AutoDock Interface after you prepare the receptor If you close the dialog box before completing the docking calculation you will need to start over Step 2 Preparing the ligand After preparing the receptor you must prepare one or more ligands to dock to it The ligand may be either in a file ora model that is open in ChemBio3D You then use AutoDock to determine the rotatable bonds and atom types in the lig and AutoDock uses this data to describe the conformational space and interaction types of the ligand To prepare the ligand 1 Inthe AutoDock Interface dialog box select the Prepare Ligand tab 2 To load a ligand do one of the following Click Browse to load a ligand into AutoDock from a file Click Import to load a ligand that is currently open as a model in ChemBio3D _ Note To import a model the model must be in the active ChemBio3D window 3 Optional Browse to or import other ligands as desired The ligands you load are listed under List Ligands 4 To determine the rotatable bonds in the ligand and its atom types click Run After determining the rotatable bonds and atom types AutoDock s
219. he atom or bond a Select the atom or bond and go to Edit gt Clear a Select the atom or bond and press DELETE Alternatively to remove a bond right click the bond and select Break Bond _ Note If automatic rectification is on you will not be able to delete hydrogen atoms Tum automatic rectification off when modifying a model Go to File gt Model Settings gt Model Building tab Atom charges Atoms are assigned a formal charge based on the atom type and bonding for that atom You can display the charge by pointing to the atom Setting charges To set the formal charge of an atom 1 Click the Build from Text tool Chapter 3 Basic Model Building 21 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 2 Select the atom s to change 3 Type lt gt or followed by the number of the formal charge 4 Press lt Enter gt To set the formal charge of an atom in a molecular fragment as you build you add the charge after the element in the text Example To build a model of a phenoxide fragment 1 Type PhO into a text box with no atoms selected 2 Press lt Enter gt The phenoxide ion molecule appears To remove the formal charge from an atom 1 Click the Build from Text tool 2 Select the charged atom 3 Type lt 0 gt 4 Press lt Enter gt Displaying charges ChemBio3D recognizes formal and delocalized charges on atoms As also shown in ChemDraw drawings ChemBio3D displays the formal charge
220. he bond between a building type and the atom type specified in the bound to type For example for C Carbonyl only double bonds can be formed to bound to type O Carboxylate If there is no bound to type specified this field is not used The possible bound to bond orders are single double triple and delocalized _ Note The bound to order should be consistent with the number of double triple and delocalized bonds for this atom type If the bound to type of an atom type is not specified its bound to order is ignored Bound to Type This specifies the building type to which the atom must be bound If there is no restriction this field is empty The Bound to type is used in conjunction with the Bound to Order field Non blank Bound to Type values CAlkene C Carbocation a C Carbonyl a C Carboxylate a C Cyclopentadienyl a C Cyclopropene a C Epoxy a C Isonitrile H Alcohol H Thiol N Ammonium N Azide Center a N Azide End N Isonitrile a C Metal CO a C Thiocarbonyl Chapter 7 Parameter Tables 142 of 318 ChemBio3D 14 0 Perkin For the Better a NNitro a O Carbonyl a OCarboxylate a O Epoxy a O Oxo a O Phosphate a P Phosphate a S Thiocarbonyl Substructures table The Substructure table Substructures xml contains a library of substructures for you to use to build models You can use a substructure as either a template to build a new fragment or to add to an existing model To attach a substructure to an exi
221. he files and parameters used in the calculation such as the size and location of the grid the atom types that will be used and other parameters for calculation of the grids The grid parameter file usually has the exten sion gpf DPF specifies the files and parameters used for the docking calculation It also includes the map files that will be used for the docking the ligand coordinate files and parameters for the search The docking parameter file usually has the extension dpf A Caution Only expert users should edit the AutoDock log files Otherwise the AutoDock calculation may produce unwanted results 1 Inthe AutoDock Interface select the Docking tab 2 Optional Click Edit GPF to edit the cavity parameters log file 3 Optional Click Edit DPF to edit the pose parameters log file 4 Click Run AutoDock After AutoDock calculates the docking AutoDock reports that the docking job is complete and asks whether you want to display the results Results dialog box appears You can review the results in the ChemBio3D structure Browser _ Note The result is saved in the AutoDock work folder in dlg file format and the default file name will be of the format lt ligand file name gt _ lt receptor file name gt _adv dlg For example if receptor pdb is the receptor name and ligand mol2 is the ligand name then the default file name of the output file is ligand_receptor_adv dlg Chapter 8 Docking 162 of 318 C
222. he measurement table To display the distance between atoms 1 Select the atoms The atoms do not have to share a bond 2 Go to Structure gt Measurements gt Display Distance Measurement Tip Alternatively you can select two atoms and hover your cursor over one of the selected atoms The pop up window displays the distance Chapter 4 Displaying Models 58 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 P e 0 23 O Alcohol 0 0 2 493A Figure 4 10 The pop up window displays the distance between atoms in separate fragments To display the angle between two bonds 1 Select either two adjacent bonds or three adjacent atoms 2 Go to Structure gt Measurements gt Display Bond Angle Measurements To display a dihedral angle 1 Select either three consecutive bonds or four consecutive atoms that make up a dihedral angle 2 Go to Structure gt Measurements gt Display Dihedral Measurement By default measurements in the Model window are displayed to one decimal place To adjust the measurement val ues 1 Go to File gt Preferences 2 Inthe Preferences dialog box select the Measurements tab 3 Inthe Display decimal places scroll box select how many digits past the decimal point you want to appear in the measurement values 4 Click OK when finished 7 Note The measurement display value you choose affects values only in the model window The measurement table The measurement table di
223. he model window is listed as a fragment in the model explorer ions may be listed as mul tiple fragments When you expand a fragment list in the model explorer the atoms the fragment contains are shown The fragment represents the highest level parent object in a model and typically represent an entire structure If your model consists of several structures the model explorer displays a fragment for each one Fragments represent sep arate parts of the model if you start at an atom in one fragment you cannot trace through a series of bonds that con nect to an atom in another fragment If you create a bond between two such atoms ChemBio3D will collapse the hierarchical structure to create one fragment Fragment objects typically consist of chains and groups but may also contain individual atoms and bonds Chains in PDB files Chains are special groups found in PDB files In ChemBio3D chains and groups are functionally identical If you rename a group as a chain or vice versa the icon will change All group commands also apply to chains Chapter 4 Displaying Models 52 of 318 hemBio3D 14 I ChemBio3 0 PerkinE For the Better Solvents The solvent object group contains all the solvent molecules in the model The individual molecules appear as child groups within the solvent object A solvent object should not be a child of any other object 7 Note When importing PDB models solvents may show up in chains ChemBio3D preserves this struct
224. header format as a non Rgroup molfile The V3000 file format is preferred over older V2000 because it a Provides better support for new chemical properties or objects and supports enhanced stereochemistry Removes fixed field widths to support large structures The fixed limits and distributed property information in the V2000 format make V2000 less than ideal for enhancing chemical representation a Supports the use of templates in a template block which is useful for representing large structures such as bio logical molecules See Template block on page 30 Consolidates property information for chemical objects Uses free format and tagging of information for easier parsing Provides better backward compatibility through BEGIN END blocks MSI MolFile The MSI MolFile is defined in Chapter 4 Chem Note File Format in the Centrum Chem Note Application doc umentation pages 4 1 to 4 5 The following is asample MSI MolFile file created using Chem3D Pro for cyclohexanol the line numbers are added for purposes of discussion only Chapter 14 File Formats 236 of 318 ChemBio3D 14 0 PerkinE For the Better MSI Molfile format Polygen 133 Polygen Corporation ChemNote molecule file 2D File format version number 90 0928 File update version number 92 0114 molecule name cyclohexanol MSI empirical formula Undefined Empirical Formula need 3D conversion 3D displacement vector 0 000 0 000 0
225. hem istry package It computes wave functions using RHF ROHF UHF GVB and MCSCF Cl and MP2 energy cor rections are available for some of these CS GAMESS is installed with ChemBio3D CS GAMESS computation features are a Minimize Energy Optimize to Transition State Compute Properties Chapter 6 Computational Engines 133 of 318 ChemBio3D 14 0 PerkinE ag For the Better Run Frequency Predict IR Raman Spectra a Predict NMR Spectra When you choose one of these options The CS GAMESS interface dialog box appears with the recommended default parameters for that computation chosen You may change parameters on any of the tabbed pages of the dialog box before running the computation If you know what parameter settings you want to use you can run any com putation using any of the options as a starting point If you are familiar with the CS GAMESS keywords you can choose Use Advanced Mode and get a GUI version of the command line interface Viewing spectra To view the predicted spectra Go to View gt Spectrum Viewer A a new tab will open in the Spectrum Viewer for each prediction that you run on a given compound Spectrum Viewer x GAMESS IR Spectrum lt x GAMESS gt Raman Spectrum lt x GAMESS gt UVVis lt x 1 UViVisible Spectrum 0 54 Absorptivity gJ 100 120 140 160 180 200 220 240 Wavelength Figure 6 11 Predicting an UV Vis spectrum for chlorobenzene using GAMESS Viewing UV
226. hemBio3D 14 0 PerkinElmer For the Better Step 7 Viewing Docking Results To view the docking results follow the steps mentioned below 1 Go to Calculations gt AutoDock Interface gt AutoDock Results 2 Inthe AutoDock Results dialog box click Prepare Results You will be asked to open the docking log file 3 Open the docking log file The file opens in ChemBio3D The results appear as a model in the ChemBio3D Model window The file includes the receptor and all poses that meet the parameters you set for the docking To view previous results 1 Inthe AutoDock Results dialog box click Browse Results under Previous Results 2 Browse to the location where you have saved the docking log file 3 Open the log file The file opens in ChemBio3D To examine the poses The docking results are displayed in the structure browser and the named group and various docking energy levels are displayed in various columns in the structure browser 1 Inthe model window ensure that the docking results model is the active tab 2 Go to View gt Structure browser All poses in the file are listed 3 Inthe structure browser select deselect checkboxes to display hide poses in the model window References See these references for more information on AutoDock The AutoDock User Guide General AutoDock FAQ AutoDock parameter suggestions a Docking and energy evaluation suggestions a Ligand limitations Chapter 8 Docking 163 of 318 p
227. hemBio3D 14 0 PerkinElmer For the Better 1 Select the dihedral angles to invert 2 Go to Structure gt Invert All of the dihedral angles that make up the ring are negated Atoms positioned axial to the ring are repositioned equat orial Atoms positioned equatorial to the ring are repositioned axial Reflecting a model Use the Reflect command to reflect through either the X Y X Z or Y Z plane or through the model origin The planes and origin are defined by the view axes not the model axes To reflect a model Go to Structure gt Reflect Model and select an option a Through X Y Plane Through X Z Plane a Through Y Z Plane Invert through Origin When you reflect your model through a plane the coordinates of the third axis are negated You can choose Invert through Origin to negate all of the Cartesian coordinates of the model If the model contains a chiral center reflection changes the model into its enantiomer In addition all the Pro R posi tioned atoms become Pro S and all the Pro S positioned atoms become Pro R All dihedral angles used to position atoms are negated f Note Pro R and Pro S in ChemBio3D are not equivalent to the specifications R and S used in standard chemistry terminology For example for the structure shown below when any atom is selected go to Structure gt Reflect Model Through X Z Plane e ge Figure 5 6 Reflecting through a plane ChemBio3D produces this enantiomer Cha
228. hin Distance of Selects all atoms except for those already selected lying Selection within the specified distance from any part of the current selection The current selection will be un selected unless multiple selection is used Select Groups within Distance of Selects all groups except for those already selected that Selection contain one or more atoms lying within the specified dis tance from any part of the current selection The current selection will be un selected unless multiple selection is used Select Atoms within Radius of Selects all atoms except for those already selected lying Selection Centroid within the specified distance of the centroid of the current selection The current selection will be un selected unless multiple selection is used Select Groups within Radius of Selects all groups except for those already selected that SelechomC ENTEN contain one or more atoms lying within the specified dis tance of the centroid of the current selection The current selection will be un selected unless multiple selection is used Chapter 12 Keyboard modifiers 220 of 318 ChemBio3D 14 0 PerkinElmer For the Better 2D to 3D Conversion This section describes how ChemBio3D performs the conversion from two to three dimensions You can open a 2D drawing using several methods Opening a ChemBioDraw or ISIS Draw document a Pasting a ChemBioDraw or ISIS Draw structure from the Clipboard a Opening a ChemBioDr
229. hing of a molecule and is scaled so as to fall between the minimum and maximum values possible for the given order The first order shape attribute counts the number of one bond paths The second order attribute counts the number of two bond paths and so on The first three orders 1 3 are available Chapter 11 Chemical properties 212 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 To calculate the shape attribute 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Shape Attribute 3 Click OK Shape Coefficient The shape coefficient is given by I D R R Where the diameter D is the maximum such value for all atoms and is held by the most outlying atom s The radius R is the minimum such value and is held by the most central atom s Examples values for D methane 0 ethane 1 propane 2 n butane 3 Example values for R Radius methane 0 ethane 1 propane 1 n butane 2 To calculate the shape coefficient 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Shape Coefficient 3 Click OK Spin Density Go to Calculations gt Compute Properties Expand Gaussian Interface and select Spin Density Click OK Oo N gt An alternative method 1 Go to Calculations gt Gaussian Interface gt C ompute Properties N Inthe Properties tab select Spin Density and click Run Sum Of Degrees Is the su
230. his information by default a Starting atomic coordinates a Starting internal coordinates a Molecular orbital energies eigenvalues a Ending atomic coordinates The workings of many of the calculations can also be printed in the out file by specifying the appropriate keywords before running the calculation For example specifying the keyword MECI shows the derivation of microstates used in an RHF 1 2 electron approximation For more information see Using keywords on page 269 F Note Close the out file while performing CS MOPAC computations or the CS MOPAC application stops func tioning Input files A CS MOPAC input file MOP is associated with a model and its dialog box settings Chapter 6 Computational Engines 131 of 318 For the Better To create a CS MOPAC input file 1 Go to Calculations gt MOPAC Interface gt Create Input File 2 Select the appropriate settings and click Create To run an input file 1 Go to Calculations gt MOPAC Interface and click Run Input File The Run MOPAC Input File dialog box appears 2 Specify the full path of the CS MOPAC file or browse to the file location 3 Select the appropriate options For more information about the options see Specifying electronic configuration on page 272 4 Click Run A new model window appears displaying the initial model The CS MOPAC job runs and the results appear All properties requested for the job appear in the out file Only iteration
231. ial force constants CalcFC a Calculate at each point CalcAll Population Analysis Options are None no options a Full same as Regular but for all orbitals a Minimum displays the total atomic charges and orbital energies a Regular displays five highest occupied and five lowest virtual orbitals with density matrices and full Mulliken population analysis Other Options By default Gaussian uses modest convergence criteria to speed up calculations The Use Tight Convergence Cri teria check box adds the keyword tight to the input template to specify full convergence You may also add a charge by first deselecting the default Use Formal Charge check box or change the Spin Multiplicity Spins can be pos itive integers Charges may be plus or minus Selecting Internal Coordinate lets you minimize only part of the model by choosing either Selected Atoms or Unse lected Atoms On the General tab set the parameters that control the output Display Every Iteration Displays the minimization process live at each iteration in the calculation f Note The Display Every Iteration parameter increases the time to minimize the structure Show Output in Notepad Sends the output to a text file Send Back Output Displays the value of each measurement in the Output window F Note The Send Back Output parameter increases the time to minimize the structure Chapter 6 Computational Engines 107 of 318 ChemBio3D 14 0
232. ialog box the prop erties are classified into categories such as GAMESS Interface and Molecular Topology 2 Expand the desired category categories and select the check boxes corresponding to the properties that you want to calculate 3 Click OK The selected properties appear in the Output window MM2 and MMFF94 MM2 and MMFF94 apply force field calculation methods These engines are designed to calculate steric energy thermal energy and other values Results are saved as part of the atom properties MM2 and MMFF94 may be viewed as different calculation techniques you use to return a result Which technique you use depends on your type of model and the properties you want to calculate MM2 MM2 is most commonly recommended for calculating properties of small organic models The MM2 procedures assume that you understand how the potential energy surface relates to conformations of your model If you are not familiar with these concepts see MM2 references on page 266 MM2 parameters The MM2 parameters are listed in the MM2Atom Types table To view the table go to View gt Parameter Tables gt MM2 Atom Types The original MM2 parameters include elements commonly used in organic compounds carbon hydrogen nitrogen oxygen sulfur and the halogens The atom type numbers for these atom types range from 1 to 50 The rest of the parameters consist of atom types and elements in the periodic table that were not included in the ori ginal MM2
233. illustrate partial charges for atoms in your model For example strongly positive charged atoms may appear bright red while strongly negative atoms appear blue Lesser positively and negatively charged atoms also appear somewhere within the color range depending on the value To display partial charges you first need to run the charge calculation To display partial charges 1 Go to File gt Model Settings and select the Colors amp Fonts tab 2 Under Color by select Atom Properties 3 Inthe Atom Properties drop down list select Charge Htckel 4 Select one of the two color bands The first band ranges from blue to red The second band has a more refined range of color 5 Inthe min max text boxes select the range of calculations you want to colorize To select the entire range of val ues Calculated for the model click Scan Value Range 6 To view the model with your options select the Preview check box at the bottom of the dialog box and click Apply 7 Click OK All the atoms are colored according to the color scale you chose Atoms with a large negative partial charge are deep blue Atoms with a large positive partial charge are deep red As the magnitude of the charges approaches 0 the color of the atom becomes paler Chapter 17 Tutorials 311 of 318 ChemBio3D 14 0 PerkinE aig For the Better T amp R ce x Figure 17 29 Partial charges for phenol For phenol the greatest negative charge is on the oxygen a
234. imate by ChemBio3D See Estim ated parameters on page 139 The parameter is derived from experimental data The parameter is well confirmed The reference for a measurement corresponds to a reference number in the References table References indicate The parameter is theorized but not confirmed where the parameter data was derived See the References parameter table for a list of references Electronegativity adjustments ChemBio3D uses the parameters in the Electronegativity Adjustments table Electronegativity Adjustments xml to adjust the optimal bond length between two atoms when one of the atoms is attached to a third atom that is Chapter 7 Parameter Tables 147 of 318 ChemBio3D 14 0 PerkinElmer For the Better electronegative For example the carbon carbon single bond length in ethane is different from that in ethanol The MM2 parameter set has one parameter for carbon carbon single bond lengths 1 523A The electronegativity cor rection parameters allow the C C bond in ethanol to be corrected The electronegativity parameter used in the Elec tronegativity Corrections table is the 1 1 6 angle type where atom type 1 is a C Alkane and atom type 6 is an O Alcohol The value of this parameter is 0 009A Thus the C C bond length in ethanol is 0 009A shorter than the stand ard C C bond length MM2 constants The MM2 Constants table MM2 Constants xml contains parameters that ChemBio3D uses to compute the MM2 force fiel
235. imine The arrows indicate A the global minimum conformation and B a local minimum conformation We now select two conformers and run the GAMESS minimization on each one We start by selecting a conformer that is above the global minimum Dihedral Driver Chart x Conformational Energy 33 0 A zT T f 32 0 gt a o c wi B 180 135 90 45 0 45 90 135 180 31 0 Chapter 17 Tutorials 314 of 318 ChemBio3D 14 0 Perkin For the Better Figure 17 33 The dihedral chart with the conformer positions shown We select point A to calculate the global min imum and point B to calculate a local minimum To run a GAMESS minimization above the global minimum 1 Inthe Dihedral Chart click a point above the global minimum for example point A in the figure above 2 Go to Calculations gt GAMESS Interface gt Minimize The GAMESS Interface dialog box opens 3 Inthe dialog box click Run The global minimum energy appears in the Output window approximately 226273 Kcal Mol To run a GAMESS minimization above a local minimum 1 Inthe Dihedral Chart click a point above a local minimum for example point B in the figure above 2 Go to Calculations gt GAMESS Interface gt Minimize The GAMESS Interface dialog box opens 3 Inthe dialog box click Run For the local minimization the result is approximately 226270 Kcal Mol The preferred conformer is lower by about 3 Kcal Mol Tutorial 12 Calculating Rotation
236. in the Perform MMFF94 Minimization dialog box select any of the following options a Display Every Iteration View the model during the calculation displaying or recording each iteration may increase the calculation time a Copy Measurements to Output Box View each measurement in the Output window a Setup new Atom Types before Calculation ChemBio3D deletes any custom MMFF94 atom types you have defined for your model Deselect this option to keep them a Setup new Atom Charges before Calculation ChemBio3D replaces custom charges you have entered in the Atom Property table To retain the custom charges deselect this option 3 Click Run The result appears in the output window Energy minimization using MM2 To minimize the energy of the molecule based on MM2 1 Set Optimal column measurements in the Measurement table go to View gt Measurement table 2 Go to Calculations gt MM2 gt Minimize Energy 3 Inthe Minimization Energy dialog box select any of these options and click Run a Minimum RMS Gradient specify the convergence criteria for the gradient of the potential energy surface Use a large values for shorter calculation time but less accurate results Use a smaller value for more accurate res ults but longer calculation time The default value of 0 100 is a reasonable compromise a Display Every Iteration view the model during the calculation displaying each iteration may slow down the cal culation a Copy Measuremen
237. inElmer Informatics or your local reseller for details About AutoDock AutoDock is an automated docking tool that helps you predict how small molecules bind to a receptor of known 3D structure ChemBio3D maintains an interface to AutoDock to perform the docking calculation AutoDock calculations are performed in several steps For further information please visit http autodock scripps edu See Docking for more information About CONFLEX CONFLEX is a conformational analysis package developed by the CONFLEX Corporation Using CONFLEX you can searche for chemically significant conformers in flexible molecules and displays the conformers as fragments in your model Conformers are reported based on the search method and energy limit that you define For further inform ation please visit www conflex us See CONFLEX for more information About Molecular Networks pKa logS and logP for predicting acid dissociation constants aqueoues solubility and octanol water distribution coef ficients of chemical compounds are computational calculator modules based on Molecular Networks chemoin formatics platform MOSES MOSES is developed maintained and owned by Molecular Networks GmbH Erlangen Germany For further information please visit www molecular networks com moses All rights reserved Molecular Networks GmbH Erlangen Germany www molecular networks com Limitations Only the following atom types and hybridization states are parameterized
238. indicated by MOPAC keywords are incompatible with MNDO d a COSMO Conductor like Screening Model solvation a POLAR polarizability calculation a GREENF Green s Function a TOM Miertus Scirocco Tomasi self consistent reaction field model for solvation PM6 applicability and limitations Parameterized Model revision 6 PM6 may be applied to all main group elements and transition metals The following apply to a PMG is a reparameterization of PM5 It has been developed using experimental and ab initio data from over 9000 compounds a PMG is a distinct improvement over PM3 and AM1 a Corrects major errors in AM1 and PM3 a More accurate prediction of heat of formation Chapter 15 References 280 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 a Generates more accurate geometries For example it optimizes anthraquinones to correct planar fused ring struc ture a More accurate positioning of bridging hydrogen bonds for example the bridging hydrogen bond between the two oxygen atoms is positioned equidistant in dicarboxylic acid anions Chapter 15 References 281 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better Online Resources PerkinElmer provides several online resources of information to help you get the most out of ChemBio3D Everything listed below is available under Online in the ChemBio3D main menu SciStore Go to Online gt Browse SciStore com Scistore com offers a variety of
239. ing Constants select the UHF wave function Note UHF calculations are typically much slower than RHF calculations Optimizing geometry ChemBio3D uses the Eigenvector Following EF routine as the default geometry optimization routine for minimization calculations The other alternatives are described below TS The TS optimizer is used to optimize a transition state It is inserted automatically when you select Optimize to Transition State from the MOPAC Interface submenu BFGS For large models over about 500 1 000 atoms the suggested optimizer is the Broyden Fletcher Goldfarb Shanno procedure By specifying BFGS this procedure will be used instead of EF LBFGS For very large systems the LBFGS optimizer is often the only method that can be used It is based on the BFGS optimizer but calculates the inverse Hessian as needed rather than storing it Because it uses little memory it is preferred for optimizing very large systems It is however not as efficient as the other optimizers Adding keywords Click the General tab to specify additional CS MOPAC keywords This will tailor a calculation to more exacting requirements For example you might use additional keywords to control convergence criteria to optimize to an excited state instead of the ground state or to calculate additional properties L7 Note Other properties that you might specify through the keywords section of the dialog box may affect the out come For more inf
240. ing on your selected preferences Chapter 17 Tutorials 286 of 318 ChemBio3D 14 0 pP PerkinElmer For the Better _ Note To view the information dialog box the following options must be selected under File gt Preferences gt Popup Info a Atom Type Measurement a Bond Length Figure 17 2 Viewing the atom label 3 Move the pointer over the C C bond to display its properties Figure 17 3 Viewing bond length To display bond angles select three atoms that are adjacent to each other 1 SHIFT click C 1 C 2 and H 7 2 Point to any of the selected atoms or their connecting bonds The angle for the selection appears Chapter 17 Tutorials 287 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Figure 17 4 Viewing bond angles To display the dihedral angle of adjacent atoms 1 SHIFT click both carbons and one hydrogen on each carbon The atoms form a dihedral angle 2 Point to any portion of the selection The dihedral angle measurement appears C 1 C 2 Length 1 5234 Order Single H 5 C 1 C 2 H 60 0 Figure 17 5 Viewing a dihedral angle You can also change the bond order In this case we can change the ethane model to ethylene 1 Click the Double Bond tool Sin the Building toolbar 2 Drag the mouse from C 1 to C 2 3 Point to the C 1 C 2 bond Notice that the bond length has decreased and the bond order has increased Chapter 17 Tutorials 288
241. ing the atom type number is the connection table for the atom You can specify up to ten other atoms The connection table for a Cartesian coordinate file can be listed in one of two ways by serial number or by position Connection tables by serial number use the serial number of each atom to determine the number that appears in the connection table of other atoms All serial numbers must therefore be unique Connection tables by position use the relative positions of the atoms in the file to determine the number for each atom that will appear in the connection table of other atoms The first atom is number 1 the second is 2 etc 6 To create multiple views of the same set of atoms you can flow the descriptions of the atoms with an equal num ber of lines corresponding to the same atoms with different coordinates ChemBio3D generates independent views using the additional sets of coordinates Cambridge Crystal Data Bank files You can import Cambridge Crystal Data Bank CCDB files but not save files in the CCDB format ChemBio3D uses the FDAT format of CCDB described on pages 26 42 of the data file specifications of the Cambridge Structural Data base Version 1 File Specifications from the Cambridge Crystallographic Data Centre For further details about the FDAT format refer to the above publication or contact the Cambridge Crystallographic Data Centre As described in the specifications of the Cambridge Crystal Data Bank format bonds ar
242. ing types whose bound to types are specified and are the same as their rectification types 3 Building types whose bound to types are not specified For example in the model depicted above O 4 could be one of several building types First it could be an O Ether atom for which the bound to type is unspecified priority number 3 above Alternatively it could be an O Alcohol for which the bound to type is the same as the rectification type H Alcohol priority number 2 above A third possibility is O Carboxyl for which the bound to type is C Carbonyl and the rectification type is H Carboxyl priority number 1 Because the characteristic of a specified bound to type that is not the same as the rectification type number 1 in the priority list above is given precedence over the other two possibilities the O Carboxyl building type is assigned to the oxygen atom Changing building types You can use a text box to change the building type and bonding characteristics For example you can change an alkane to an alkene To change the building type of some atoms 1 Click a carbon atom using the Build from Text tool A text box appears 2 SHIFT click an adjacent carbon atom Both atoms are selected 3 Click inside the text box and type C Alkene 4 Press ENTER The building type and the bond order are changed to reflect the new model You can point at the atoms and bonds to display this new information Chapter 5 Building Advanced Models
243. inus 2 electrons Sparkles are represented in ChemBio3D by adding a charged dummy atom to the model a Tip Dummy atoms are created with the uncoordinated bond tool You must add the charge after creating the dummy The output file shows the chemical symbol as XX Approximate Hamiltonians in MOPAC There are five approximation methods available in CS MOPAC MNDO AM1 a PM3 PM6 MNDO d The potential energy functions modify the HF equations by approximating and parameterizing aspects of the Fock mat rix The approximations in semiempirical MOPAC methods play a role in the following areas of the Fock operator a The basis set used in constructing the 1 electron atom orbitals is a minimum basis set of only the s and p Slater Type Orbitals STOs for valence electrons a The core electrons are not explicitly treated Instead they are added to the nucleus The nuclear charge is termed Neffective Chapter 15 References 277 of 318 ChemBio3D 14 0 Perkin For the Better For example Carbon as a nuclear charge of 6 2 core electrons for a effective nuclear charge of 4 a Many of the 2 electron Coulomb and Exchange integrals are parameterized based on element Choosing a Hamiltonian Overall these potential energy functions may be viewed as a chronological progression of improvements from the old est method MINDO 3 to the newest method PM6 However although the improvements in each method were designed to make global
244. io3 0 PerkinElmer For the Better PEG Qualty Trarnparent Background FI s Coke Space Pheed Scale Proels S Animon No Frane Number of Frames 2 9 GIF Figure 14 4 Save as GIF dialog box Graphic file formatting uses CxImage an open source toolset under the zlib license 1 WMF and EMF ChemBio3D supports the Windows Metafile and Enhanced Metafile file formats These are the only graphic formats as opposed to chemistry modeling formats that can be used for import They may also be used for export EMF by using the Save As File menu command or the clipboard and WMF by using the clipboard only See Copying as a static image on page 29 for more information EMF files are exported with transparent back grounds when this is supported by the operating system Windows 2000 and Windows XP The WMF and EMF file formats are supported by applications such as Microsoft Word for Windows f Note ChemBio3D does not embed structural information in models exported as EMF files If you have EMF files produced with previous versions you can still open them in ChemBio3D and work with the structure However EMF files saved from an earlier version Chem3D 8 0 contain graphic information only and cannot be opened in ChemBio3D BMP The Bitmap file format saves the bitmapped representation of a ChemBio3D picture The Bitmap file format enables you to transfer ChemBio3D pictures to other applications such as Microsoft Word for
245. ion mone HOMO LUMO Energies lonization Potential LOCALIZE Print localized orbitals VECTORS Print final eigenvectors molecular orbital coefficients BONDS Bond Order Matrix Chapter 15 References 271 of 318 hemBio3D 14 I ChemBio3D 14 0 PerkinElmer For the Better The following table contains the keywords that invoke additional computations Terms marked with an asterisk appear in the out file CIS UV absorption energies Performs C I using only the first excited Singlet states and does not include the ground state Use MECI to print out energy information in the out file FORCE Vibrational Analysis Useful for determining zero point ener gies and normal vibrational modes Use DFORCE to print out vibration information in out file NOMM No MM correction By default MOPAC performs a molecu lar mechanics MM correction for CONH bonds i Resolve density matrix into sigma and pi bonds PRECISE Increase SCF criteria Increases criteria by 100 times This is useful for increasing the precision of energies reported T n M H D Increase the total CPU time allowed for the job The default is 1h 1 hour or 3600 seconds Specifying electronic configuration MOPAC must have the net charge of the molecule in order to determine whether the molecule is open or closed shell If a molecule has a net charge be sure you have either specified a charged atom type or added the charge You can assign a
246. ional Engines 128 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 0 03463 0 07896 0 07815 0 01046 0 05488 0 05329 You can reason from the result shown that the unpaired electron in the ethyl radical is more localized at P orbital on C1 Generally this is a good indication of the reactive site Example 8 RHF spin density This example uses an ethyl radical to calculate the RHF spin density 1 To create the radical click in the model window A text box appears 2 Type EtH and press ENTER 3 Click the Select tool 4 Select H 8 5 Press Backspace to remove the H 8 hydrogen If automatic rectification is on a message appears asking to turn it off to perform this operation 6 Click Turn Off Automatic Rectification The Ethyl Radical is displayed 7 Go to Calculations gt MOPAC Interface gt Minimize Energy 8 On the Theory tab choose PM3 and Closed Shell Restricted Chapter 6 Computational Engines 129 of 318 hemBio3D 14 I ChemBio3D 14 0 PerkinElmer For the Better 9 On the Properties tab choose Spin Density 10 Click Run The Message window displays the total spin densities for each atom spin densities for all orbitals are totaled for each atom f Note You can look in the out file for a breakdown of the spin densities for each atomic orbital 0 00001 You can reason from this result that the unpaired electron in the ethyl radical is more localized on C1 Generally thi
247. ions R and Raman spectra predictions Multi step jobs a Partial optimizations Support for DFT methods Advanced mode Using Gaussian ChemBio3D can predict NMR IR Raman and UV VIS spectra To calculate a spectrum go to Cal culations gt Gaussian Interface and select the spectrum you want f Note Depending on your computer s speed and memory and the size of the model Gaussian calculations may take several minutes Tip Run a minimization before predicting spectra MM2 is faster than Gaussian minimization and is usually adequate Gaussian may fail to produce a spectrum if the model is not at a minimum energy state Viewing spectra To view the predicted spectra Go to View gt Spectrum Viewer A a new tab will open in the Spectrum Viewer for each prediction that you run on a given compound Chapter 6 Computational Engines 104 of 318 hemBio3D 14 I yee A PerkinElmer For the Better Figure 6 4 Predicted spectra for chlorobenzene o Tip Using the spectrum viewer you can view spectra produced by computational engines besides Gaussian See CS GAMESS on page 133 for an example Multi step jobs You can link jobs and run them with one command There is no limit to the number of jobs that can be linked To run multiple jobs 1 To select your first job usually Minimization go to Calculations gt Gaussian Interface and select the job you want 2 Click the button and use the Job Type drop down lis
248. irection of the drag the axis of rotation is orthogonal to the drag axis inthe plane of the screen The Rotate tool rotates the view only it does not change atoms Cartesian coordin ates To rotate around an axis 1 With the Rotate tool selected move the cursor to the top edge of the model window The rotation bars appear 2 Click drag the rotation bar at the top of the model window The model rotates around the Z axis 3 Optional Click drag the right and bottom rotation bars to rotate the model around the X and Y axes _ Note Rotation bars appear only when you use the Rotate tool To rotate around a bond 1 Click the Select tool R in the Building toolbar 2 Select a bond in your model 3 Select the Rotate tool 4 Click drag the Rotate About Bond rotation bar Bill on the left side of the Model window Bond and atom properties Many model properties are available at a glance Hover the cursor over any bond or atom to view its properties F Note To choose the properties that appear go to File gt Preferences In the Popup Info tab select the popup information you want shown To see bond and atom properties of ethane 1 Click the Select tool La in the Building toolbar 2 Move the cursor over a carbon atom An information box appears next to the atom By default the first line contains the atom label either C 1 or C 2 The second line shows the name of the atom type C Alkane Other information may appear depend
249. irs around a particular atom type Notice that an amine nitrogen atom type number 8 has one lone pair and an ether oxygen atom type number 6 has two lone pairs Lone pairs are treated explicitly for atoms such as these which have distinctly non spherical electron Chapter 7 Parameter Tables 150 of 318 ChemBio3D 14 0 Perkin For the Better distributions For atom types such as O Carbonyl which have more nearly spherical electron distributions no explicit lone pairs are necessary Note Lone pairs are not automatically displayed in atoms that require them Torsional parameters The Torsional Parameters table Torsional Parameters xml contains parameters used to compute the portions of the MM2 force field for the torsional angles in your model The 4 Membered Ring Torsional Parameters 4 membered Ring Torsionals xml contains torsional parameters for atoms in 4 membered rings Each record in the Torsional Parameters table and the 4 Membered Ring Torsional Parameters table consists of six fields Dihedral Type V1 V2 V3 Quality and Reference Dihedral Type The Dihedral Type field contains the atom type numbers of the four atom types that describe the dihedral angle For example angle type 1 2 2 1 is a dihedral angle formed by an alkane carbon bonded to an alkene carbon that is bon ded to a second alkene carbon which in turn is bonded to another alkane carbon In other words angle type 1 2 2 1 is the dihedral angle between the two
250. is the optimization flag for the bond angle specified in Column 4 a Column 6 is the dihedral angle for the connectivity specified in Column 8 Column 7 is the optimization flag for the dihedral angle specified in Column 6 5 To specify particular coordinates to optimize change the optimization flags in Column 3 Column 5 and Column 7 for the respective internal coordinate The available flags in MOPAC are Optimize this internal coordinate fo Do not optimize this internal Reaction coordinate or grid index Monitor turning points in DRC 6 Add additional information in line Ln 1 For example symmetry information used ina SADDLE computation 7 Leave the last line in the data file blank to indicate file termination 8 Save the file in a text only format MOPAC Graph files A MOPAC Graph GPT file stores the results of MOPAC calculations that include the GRAPH keyword It contains the final geometry electronic structure and other properties of the molecule ChemBio3D supports the MOPAC Graph file format for import only Protein Data Bank files Brookhaven Protein Data Bank files PDB ENT are used to store protein data and are typically large in size The PDB format provides the primary sequence of protiens ChemBio3D can import PDB and ENT file types and export Chapter 14 File Formats 263 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better PDB The PDB file format is taken from the Protein Data Bank Atomic Coordi
251. isable any of the following features under the Window Settings section Tabbed windows This enables each open file to be represented as a tab in the model window Chapter 2 ChemBio3D Basics 9 of 318 hemBio3D 14 I sneme 9 PerkinElmer For the Better a Sliding windows This enables other windows such as Structure Browser and Model Explorer to slide in and out of the ChemBio3D If unchecked the windows will appear or disappear with no sliding a Sliding window animation This enables animation for the sliding window Message in Output box This displays message in the Output box at the bottom of the ChemBio3D F Note You may need to close and restart ChemBio3D to activate these features 6 Click OK Background settings To set background color effects and picture go to File gt Model Settings gt Background tab Your changes apply only to the current model window unless Set as Default is clicked Sample files ChemBio3D includes a variety of sample files to help you learn how to build and study molecular models including bio logical and inorganic structures To open a sample file go to File gt Sample Files and select a file from one of the following groups a Bio Demo a Docking a Drug a Inorganic Nano File Edit View Structure Calculations Surfaces Onlin D New CtrleN Be By Sample Files Bio gt 9 Open Ctri O Demo gt gt Cloud gt Docking Drug d Import Fil Inorganic gt
252. itions and angles of atoms in the model relative to the origin atom Measurements Displays the distance between two selected atoms the angle formed by three selected atoms or the dihedral angle formed by four selected atoms Bond Length Displays the distance in angstroms between the atoms attached by a bond Bond Order Displays the bond orders calculated by Minimize Energy Steric Energy or Molecular Dynamics Chapter 4 Displaying Models 43 of 318 ChemBio3D 14 0 PerkinElmer For the Better Bond orders are usually Single Double or Triple depending on whether the bond is a single double or triple bond Computed bond orders can be fractional f Note Precise bond orders for delocalized pi s ystems are displayed if the MM2 Force Field has been calculated Partial Charge Displays the partial charge according to the currently selected calculation See Surface types on page 62 for information on how to select a calculation Group Name Displays the group name if the selected atom is part of a group Show MM2 Bond Order Instead of ChemBio3D Bond Order Displays the bond order based on MM2 cal culations Show Customized Atom Properties Shows properties that are listed in the columns of the Atom Property table To view the Atom Property table go to View gt Atom Property Table The columns are populated by a variety of meth ods e g running an MM2 minimization Showing hydrogen bonds ChemBio3D can detect and display hydrog
253. kcal mole repulsive interaction 35 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Ribbons These models show large protein molecules in a form that highlights secondary and tertiary structure Ribbon models can be colored by group to identify the amino acid constituents Your model must have a protein backbone to display ribbons Cartoons Cartoon models like ribbon models show large protein molecules in a form that highlights secondary and tertiary structure Ribbon and Cartoon model display modes do not provide pop up information and are not intended for printing as bitmaps Atom and bond size You can adjust the size of atoms and bonds in ball and stick cylindrical bonds and space filling models Go to File gt Model Settings The Model Settings dialog box appears Select the Atom amp Bond tab To view your changes before you apply them select Preview Toadjust the atom size move the Atom Size slider Toadjust the bond size move the Bond Size slider Click OK Oo na BR WD The Atom Size value 0 small to 100 large is a percentage of the covalent radius specified for each atom in the Ele ments table When the Atom Size is 100 the atoms are scaled to their maximum radii The value of this setting affects Ball and Stick and Cylindrical Bond models f Note To open the Elements table go to View gt Parameter Tables gt Elements Displaying dot surfaces You can add dot surfaces to
254. l angle measurements are added to the Measurement table To help keep visual track of the atoms as you change the dihedral angle you can display the serial numbers and element symbols for the selec ted atoms 2 Inthe Measurement table select the Display check box for one of the listed dihedral angles such as H 3 C 1 C 2 H 8 f Note To view in the model which atoms you are selecting in the Measurements window go to View gt Model Display and select Show Serial Numbers and Show Atom Symbols 3 Click the arrow next to the Rotate tool EMI and tear off the rotation dial by dragging on the blue bar at the top 4 At the bottom of the Rotation Dial select either dihedral rotation button 5 Do one of the following a Enter the value 0 0 in the degrees display box Chapter 17 Tutorials 297 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 b Click and drag the green button on the rotation dial to 0 0 Figure 17 12 Rotating a dihedral angle To compute steric energy 1 Go to Calculations gt MM2 gt Compute Properties _ Note The property tab defaults should remain as in the previous calculation 2 Click Run The final line in the Output box appears MMZ Calculation completed successfully Stretch 0000 Bend 0005 Stretch Bend 0000 Torsion 1330 Non 1 4 VDW 0000 1 4 VDW 7726 Total Energy 9061 kcal mol The total energy for this frame 3 906 kcal mol Calculation ended Figure 17
255. l appears in the model window as you draw your structure Alternatively you can draw a structure using ChemBioDraw and paste the structure into the ChemDraw panel 1 Draw a structure in ChemBioDraw 2 Copy the structure to the clipboard 3 In ChemBio3D go to Edit gt Paste or type CTRL V in the ChemDraw panel For more information see The ChemDraw panel Using other 2D drawing packages In ChemBio3D you can also use 2D structures drawn in 2D drawing packages other than ChemDraw When you draw models using these packages a The standard measurements are applied to the model For more information see 2D to 3D Conversion on page 221 a ChemBio3D ignores objects such as arrows orbitals and curves copied to the clipboard Chapter 3 Basic Model Building 15 of 318 ChemBio3D 14 0 PerkinElmer For the Better Superatoms in ISIS Draw are expanded if ChemBio3D finds a corresponding substructure Otherwise you must define a substructure See Defining substructures on page 24 Building from text A simple way to create a model is to enter a text string that represents the structure for the model you want to build You can enter the text as either the structure name formula InChI or SMILES string Here are a few examples Name Tyrosine Iron III Phosphate Formula CH3CH2COOPH2 CH3 CH2 2COO NH4 a SMILES string oc C H 01 C H O CCH O C H O C H 0 1 InChl string InCchI 1 C8H7C10 c1 6 10
256. lding types In a few instances you may want to define your own building types whether to add to the building types table for build ing or to add to a file format interpreter for importing To define your own building types Chapter 5 Building Advanced Models 83 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 1 Go to View gt Parameter Tables gt Chem3D Building Atom Types The Chem3D Building Atom Types table opens in a window 2 To edit a building type click in the cell that you want to change and type new information 3 Enter the appropriate data in each field of the table Be sure that the name for the parameter is not duplicated else where in the table 4 Close and save the table You now can use the newly defined building type Stereochemistry You can alter the stereochemistry of your model by inversion or reflection Inversion Inversion repositions side chains extending from a chiral atom that you select For example assume you want to invert N methylcyclohexylamine around the C 2 carbon highlighted below Figure 5 4 N Methylcyclohexylamine with the C 2 atom selected The inverted structure becomes Figure 5 5 Inverted N Methylcyclohexylamine model To invert symmetry around a chiral atom 1 Select the atom 2 Go to Structure gt Invert To invert several dihedral angles such as all of the dihedral angles in a ring simultaneously Chapter 5 Building Advanced Models 84 of 318 C
257. le is a binary or ASCII file that is used as an input for other graphical visualization programs such as ChemBio3D Chapter 15 References 265 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better MM2 references This section provides additional information about the MM2 parameters and force field that has not be covered in other areas of the ChemBio3D documentation MM2 parameters The MM2 parameters were derived from three sources a Most of the parameters were provided by Dr N L Allinger a Several additional parameters were provided by Dr Jay Ponder author of the TINKER program a Some commonly used parameters that were not provided by Dr Allinger or Dr Ponder are provided by Perkin Elmer However most of these parameters are estimates which are extrapolated from other parameters The best source of information on the MM2 parameter set is Molecular Mechanics Burkert Ulrich and Allinger Nor man L ACS Monograph 177 American Chemical Society Washington DC 1982 A method for developing reasonable guesses for parameters for non MM2 atom types can be found in Development of an Internal Searching Algorithm for Parameterization of the MM2 MM3 Force Fields Journal of Computational Chemistry Vol 12 No 7 844 849 1991 The MM2 force field ChemBio3D includes a new implementation of Norman L Allinger s MM2 force field based in large measure on work done by Jay W Ponder of Washington University This chapt
258. le manually Any mistake in the manual editing may block AutoDock from performing the docking job correctly 9 Click Run AutoDock saves the results in the AutoDock work folder A report of the results and any errors that may have occurred appear at the bottom of the AutoDock Interface dialog box Toclear the window click Clear Log Tosave the log to file click Save Log a To change the folder in which the files are saved click Browse Work Folder Step 5 Selecting pose parameters Prepare DPF During the docking calculation AutoDock determines each possible pose the ligand can undergo and chooses the best poses to use The pose parameters you enter determine how AutoDock will use the poses to calculate the docking No of Individuals in Population This is the number of individuals in the population Each individual is a coupling of a genotype and its associated phenotype The number must be a positive integer Typical values that are often used range from 50 to 150 Generations The number of times a new breed of molecules is created using Generic Algorithm rules from the pre vious generation Larger molecules will need more generations The number must be a positive integer The default value is 27000 Typical values that are often used range from 5000 to 30000 Run time for each molecule increases lin early with this number Energy Evaluations Upper limit on the total number of energy evaluations performed in a single GA run
259. llowing is asample SMD file produced using Chem3D Pro for cyclohexanol the line num bers are added for purposes of discussion only Line 1 gt srrr Cyclohexane Line 2 DTCR Chem3D 00000 05 MAY 92 12 32 26 Line 3 gt cT Cyclohexan 00039 Line 19 19 A2 512 613 Line Line Line Line Line Line Line Line Line Line Line Line Line Rosdal is a product of Softron Inc 2SMD format H Bebak AV IM AM Bayer AG Chapter 14 File Formats 247 of 318 ChemBio3D 14 0 For the Better Line Line 19 Line 20 Line 21 Line 22 Line 23 Line 24 Line 25 Line 26 Line 27 Line 28 Line 29 Line 30 Line 31 Line 32 Line 33 Line 34 Line 35 Line 36 Line 37 Line 38 Line 39 Line 40 Line 41 Line 42 Line 43 ANGSTROEM 0020 Line 44 Line 45 Line 46 Line 47 Line 48 Line Chapter 14 File Formats 248 of 318 ChemBio3D 14 0 Perkin For the Better 5270 18551 9815 4047 19321 10636 2794 2876 14029 22477 806 14642 23341 1740 Each line is either a blank line a block header line or a data record containing multiple fields of information about the structure The SMD file is broken down into several blocks of information The header for each block starts with a gt sign Individual fields are delimited by space s or a tab The fields in the SMD format file used by Chem3D Pro are discussed below 1 Line 1 star
260. lohexane there are six equivalent local minima twisted boat two equivalent global minima chair and many transition states one of which is the boat conformation Finding the global minimum is extremely challenging for all but the most simple molecules It requires a starting con formation that is already in the valley of the global minimum not in a ocal minimum valley The case of cyclohexane is straightforward because the global minimum is either of the two possible chair conformations To obtain the new starting conformation change the dihedrals of the twisted conformation so that they represent the potential energy val ley of the chair conformation The most precise way to alter a dihedral angle is to change its Actual value in the Measurement table when dihedral angles are displayed An easier way to alter an angle especially when dealing with a ring is to move the atoms by dragging then cleaning up the resulting conformation To change a dihedral angle 1 Drag C1 below the plane of the ring The cursor appears as a box with a hand 2 Drag C4 above the plane of the ring While you drag an atom the bond lengths and angles become deformed To return them to the optimal values before minimizing select the model by dragging a box around it with the Select tool and run Clean Up Now run the minimization 1 Goto Calculations gt MM2 gt Minimize Energy and click Run Allow the minimization to finish 2 Reorient the model using the
261. lorer Otherwise Name gt Struct generates the structure and fragment1 appears 5 Click in the model window again to open another text box 6 Inthe text box Replace the word Epinephrine with Methamphetamine and press ENTER Methamphetamine appears in the model explorer Figure 17 16 Two fragments If the two fragments are jumbled together consider separating them so that the overlay results are clear To move one of the fragments 1 Click the fragment name in the model explorer 2 Using the Move Objects tool e click drag the fragment in the model window To overlay the fragments 1 Using the Move Objects tool Ea click an empty region of the model window to deselect all fragments 2 Inthe model explorer window click the epinephrine fragment to select it 3 Right click the fragment in the model explorer and go to Overlay gt Set Target Fragment The fragment is selected as the target g Note To deselect a fragment as the target go to Overlay gt Clear Target Fragment Model Explorer a x FA Epinephrine F Methamphetamine Figure 17 17 Model explorer with target selected Chapter 17 Tutorials 302 of 318 ChemBio3D 14 0 PerkinElmer For the Better 4 Inthe model explorer window right click the methamphetamine fragment 5 Go to Overlay gt fast overlay on the context menu The fragments are overlaid Figure 17 18 Overlaid fragments Tutorial 7 Aligning Models The Align com
262. low contains keywords sent to CS MOPAC and some other keywords you can use to affect con vergence Chapter 6 Computational Engines 113 of 318 i 14 I Ghembios 9 PerkinElmer For the Better Automatically sent to CS MOPAC to specify the use of the Eigenvector Following min imizer GEO OK Automatically sent to CS MOPAC to override checking of the Internal coordinates MMOK Automatically sent to CS MOPAC to specify Molecular Mechanics correction for amide bonds Use the additional keyword NOMM to tum this keyword off The maximum ratio of calculated predicted energy change The default is 4 0 The minimum ratio of calculated predicted energy change The default value is 0 000 PRECISE Runs the SCF calculations using a higher precision so that values do not fluctuate from run to run Overrides safety checks to make the job run faster or further RECALC 5 Use this keyword if the optimization has trouble converging to a transition state For descriptions of error messages reported by CS MOPAC see the MOPAC manual To interrupt a minimization in progress click Stop Example This example shows how to locate the eclipsed transition state of ethane Build a model of ethane Go to File gt New Double click in the model window A text box appears Type CH3CH3 and press ENTER A model of ethane appears Select the Rotation tool oan A OO N gt Click the arrow next to the Rotation tool and drag down the
263. ls displayed To display symbols for all atoms do one of the following a Goto View gt Model Display gt Show Atom Symbols a Click the Atom Symbol icon on the Model Display toolbar a Right click an empty area of the model window and select Show Atom Symbols in the context menu To display symbols for selected atoms 1 Select the atoms in the model window O Tip You can also select the atoms in the model explorer Either SHIFT click or CTRL click the atoms from the list 2 Right click one of the selected atoms A context menu appears 3 Go to Atom Symbols gt Show Atom Symbols Chapter 4 Displaying Models 39 of 318 ChemBio3D 14 0 PerkinE For the Better To set the appearance of atom symbols to their defaults 1 Go to File gt Model Settings 2 On the Colors amp Fonts tab select the atom label font point size and color 3 Click Set as Default All atoms currently in the model window display the selected options 4 Click OK f Note The default appearance setting also affects the serial number Rotating models By default when you rotate a model all objects in the model window rotate together However ChemBio3D provides many options for rotating objects You can rotate each fragment or part of a fragment rotate objects around axes a specified bond or a dihedral bond Free rotations You can freely rotate your entire model to any angle around any axis To freely rotate a model 1 Select the Rotate
264. lso float the panel any where on your screen or dock it to the ChemBio3D user interface Right click the ChemDraw panel title bar and select either Docking or Floating You can also click on the ChemDraw panel title bar and drag it to any of the standard dock ing orientations Linking the 2D and 3D Views The ChemDraw panel and model window have two linking modes LiveLink and Insertion In LiveLink mode any model you build in the model window appears in the ChemDraw panel Conversely any structure you draw in the ChemDraw panel appears in the model window The ChemDraw panel title bar shows which mode is active The linking options appear just below the title bar Insertion mode options are Chapter 2 ChemBio3D Basics 6 of 318 ChemBio3D 14 0 PerkinElmer For the Better Link Mode toggle between LiveLink mode and Insertion mode Clear clear the structure in the ChemDraw panel Add or Replace contents in ChemDraw panel the default function is to replace Chemical names SMILES create a model by typing a compound name or SMILES string into the Name Struct box Group name specify the group name of the compound to be added or replaced Group ID specify the group ID of the compound to be added or replaced Draw gt 3D ADD This option is available if these conditions are met A valid Group name and Group ID for the compound is specified Astructure appears in the ChemDraw Insertion Panel a The specified ID value is numeric
265. lumn 4 Right click in the cell and choose Paste from the context menu The content will be not be visible until you move to another cell 5 Select the cell in the Name column 6 Type aname for the substructure 7 Close and save the Substructures table An example Consider an ester substructure R COOR You can build this substructure as part of the model below Chapter 3 Basic Model Building 24 of 318 ChemBio3D 14 0 PerkinElmer For the Better Select atoms 3 5 the two oxygen atoms and the carbon atom between them and using the instructions above create a new record in the Substructures table To append an ester onto the end of the chain as a carboxylic acid double click a hydrogen to replace it with the ester as long as the name of the substructure is in the text box Replacing H 8 of the original structure would produce this structure w Notice that the carbon atom in the ester has replaced the hydrogen This is because when the ester was defined the carbon atom had a lower serial number 3 than the oxygen atom that formed the other attachment point in the sub structure 5 F Note When defining substructures with multiple attachment points note the serial numbers of the atoms in the substructure so that you can correctly orient the substructure when it is inserted in the model For more inform ation see Attachment point rules on page 26 Advantages of using substructures Here are some advan
266. lvent The change in boiling point is calculated using the formula ATp Kpm Where K5 is the molal boiling point constant m is the concentration of the solute expressed as molality and AT is the change in temperature To report the boiling point 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Boiling Point 3 Click OK p C_ is the heat capacity at constant pressure It is defined as a differential quantity the ratio of a small amount of heat 6Q added to the body to the corresponding small increase in its temperature 6T as shown in formula Chapter 11 Chemical properties 190 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 o 54 C Where a C is the heat capacity at constant pressure a Q is the small amount of heat added to the body OT is the change in temperature pis the pressure Uis the partial change in internal energy Vis the partial change in volume Tis the partial change in temperature To calculate Cy 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Cp 3 Click OK v C is defined as the heat capacity at constant volume When heat dQ is introduced into the system the change in its internal energy OU is 0U 6Q poV If the process is performed at constant volume the relation becomes A 21 7 S To calculate C 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and sel
267. m The help will begin with a message such as Help on class Atom in module ChemScript14 Enter SMILES Data You can also test to verify that ChemScript is working correctly One common use for ChemScript is to apply func tions to SMILES strings For example you can assign a SMILES string to a variable Type the following line and press lt Enter gt myMol Mol LoadData C1CCCCC1C This message appears Open molecule successfully chemical x smiles Reporting a Chemical Name You can now use the variable to report the chemical name For example at the command prompt type the line below and press Enter myMol chemicalName The line methylcyclohexane is returned Counting Atoms To count the atoms in the string type the following line and press lt Enter gt myMol CountAtoms The command returns the atom count for the structure defined with the chemical x smiles format for C1CCCCC1C which is 7 Exiting IDLE To exit type this line and press lt Enter gt exit Confirm any prompts to complete the exit command Python IDLE exits Getting Started Guide ChemScript includes a Getting Started guide to help you begin developing and using your own scripts To open the guide go to Start gt All Programs gt ChemBioOffice2014 gt ChemScript 14 0 gt Getting Started The document includes notes on the ChemScript objects and functionality Python and an overview of examples installed Editing Scripts Using IDLE or
268. m calculation when necessary Charge Dipole interaction term Allinger s potential function includes one of two possible electrostatic terms one based on bond dipoles or one based on partial atomic charges The addition of a charge dipole interaction term allows for a combined approach where partial charges are represented as bond dipoles and charged groups such as ammonium or phosphate are treated as point charges Quartic stretching term With the addition of a quartic bond stretching term troublesome negative bond stretching energies which appear when long bonds are treated by Allinger s force field are eliminated The quartic bond stretching term is required primarily for molecular dynamics it has little or no effect on low energy conformations To precisely reproduce energies obtained with Allinger s force field set the quartic stretching constant in the MM2 Constants table window to zero Electrostatic and van der Waals cutoff terms The cutoffs for electrostatic and van der Waals terms greatly improve the computation speed for large molecules by eliminating long range interactions from the computation To precisely reproduce energies obtained with Allinger s force field set the cutoff distances to large values greater than the diameter of the model The cutoff is implemented gradually beginning at 50 of the specified cutoff distance for charge and charge dipole interactions 75 for dipole dipole interactions and 90 for v
269. m of degrees of every atom An atom s degree is the number of nonhydrogen atoms to which it is bonded To calculate the sum of degrees 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Sum of Degrees 3 Click OK Chapter 11 Chemical properties 213 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Sum of Valence Degrees Is the sum of degrees of every atom An atom s valence degree is equal to the sum of its adjacent bonds orders including hydrogens To calculate the sum of valence degrees 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Sum of Valence Degrees 3 Click OK Thermodynamic Energy To calculate thermodynamic energy using Gaussian 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select Thermodynamic Energy 3 Click OK Topological Diameter Is the longest dimension of a molecule To calculate the topological diameter 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Topological Diameter 3 Click OK Total Connectivity Is the connectivity considered over all the heteroatoms To calculate the total connectivity 1 Go to Calculations gt Compute Properties 2 Expand Molecular Topology and select Total Connectivity 3 Click OK Total Energy Is the sum of kinetic energy and potential energy To calculate total energy using GAMESS 1 Go to Calcul
270. mBioDraw Struct Name feature to generate structures from chemical names and names from their struc tures Molecular Mechanics Optimize molecular structures using the MM2 force field The ChemScript API online PerkinElmer also provides the documentation of the API online You can find the API at sdk cambridgesoft com Tutorials We provide several sample scripts to illustrate how you can develop your own custom code to meet your business needs Many of the scripts we use are in the ChemScript samples directory By default this directory is where ChemBioOffice 2014 auxillary files are installed On Windows 7 and 8 C ProgramData CambridgeSoft ChemoOffice2014 ChemScript Examples Premium functionality that may be licensed from PerkinElmer Chapter 10 ChemScript 185 of 318 ChemBio3D 14 0 Perkin For the Better For the sake of brevity we won t repeat the scripts in this manual or try to teach Python However we briefly describe what you can do with the code examples so that you can modify and expand upon them for your own use As you read the tutorials you are encouraged to view the code in IDLE and edit it as desired to see how each example works For more on IDLE see Getting Started on page 182 Example 1 Automated Structure Clean up This sample script cleans up the structures in multiple ChemBioDraw files all at the same time It uses the same cleanup function that is in ChemBioDraw The script is in the directory Ex
271. mand lets you position a fragment in a desired orientation and proximity relative to a second fragment Each fragment remains rigid during the alignment computation The Align command is available when two or more distances between atoms in one fragment and atoms in a second fragment are specified These distances are entered into the Optimal field in the Measurement table You can use alignment to simulate the association of regions of similar lipophilicity and hydrophilicity on two prox imate polymer chains In this tutorial we demonstrate the Align command using two polymer chains Build the first polymer chain 1 Open a new Model window and select the Build from Text tool A 2 Click in the model window A text box appears 3 Type AA mon 3 C2F4 4 AA mon 3H in the text box 4 Press ENTER A polyacrylic acid polytetrafluoroethylene block copolymer appears in the model window The text AA mon 3 is con verted to a polymer segment with three repeat units of acrylic acid The text C2F4 4 is converted to a polymer seg ment with four repeat units of tetrafluoroethylene Build a copy of the chain Click in the model window well above and to the right of the first model When the filled text box appears press ENTER A second polymer molecule appears Orient the chains 1 Click inthe empty space in the model window to de select any atoms in the model window Chapter 17 Tutorials 303 of 318 pP PerkinElmer For the Better
272. mat for each line containing internal coordinate data in the MOPAC Data File is FORMAT 1X 2A 3 F 12 6 13 1X 314 Protein Data Bank files The Protein Data Bank file format Protein DB is taken from pages 3 14 15 and 17 18 of the Protein Data Bank Atomic coordinate and Bibliographic Entry Format Description dated January 1985 A Protein Data Bank file can contain as many as 32 different record types Only the COMPND ATOM HETATM and CONECT records are used by ChemBio3D all other records in a Protein Data Bank file are ignored The COMPND record contains the name of the molecule and identifying information The ATOM record contains atomic coordinate records for standard groups and the HETATM record contains atomic coordinate records for non standard groups The CONECT record contains the atomic connectivity records F Note The COMPND record is created by ChemBio3D to include the title of a ChemBio3D model only when you are Saving a file using the Protein Data Bank file format This record is not used when opening a file The following is an example of a Protein Data Bank Output File from ChemBio3D for L Alanine COMPND Alanine pdb HETATM o HETATM 0 HETATM 0 6 HETATM 2 HETATM O53 Chapter 14 File Formats 243 of 318 ChemBio3D 14 0 Perkin For the Better HETATM HETATM HETATM HETATM HETATM HETATM HETATM HETATM CONECT CONECT CONECT CONECT CONECT CONECT CONECT
273. messages appear for these jobs Note If you open a CS MOPAC file that includes a model with an open valence you can prevent ChemBio3D from readjusting the coordinates by turning off Automatically Rectify in the Building control panel f Note CS MOPAC input files with multiple instances of the Z matrix under examination will not be correctly dis played in ChemBio3D This type of CS MOPAC input files includes calculations that use the SADDLE keyword or model reaction coordinate geometries Running CS MOPAC jobs ChemBio3D lets you select a CS MOPAC job description file JDF The JDF file can be thought of as a set of Set tings that apply to a particular dialog box To create a JDF file 1 Go to Calculations gt MOPAC Interface gt Create Input File and choose a calculation 2 After all settings for the calculation are specified click Save As To run a CS MOPAC job from a JDF file 1 Go to Calculations gt MOPAC Interface and click Run MOPAC Job The Open dialog box appears 2 Select the JDF file to run The dialog box corresponding to the type of job saved within the file appears 3 Click Run After you perform a CS MOPAC calculation you can repeat the job as follows 1 Go to Calculations gt MOPAC Interface and choose Repeat name of computation The appropriate dialog box appears 2 Change parameters if desired and click Run The calculation proceeds Creating structures from ARC files When you perform a CS MOPAC calculatio
274. metry The Gaussian Interface dialog box appears with Minimize as the default Job Type 2 Choose the defaults on the Jobs tab or set your own parameters Following are the different fields available in the Jobs tab Job Type Sets defaults for different types of computations Method Selects a method Basis Set Specifies the basis set Most methods require a basis set to be specified See the Gaussian Help file for exceptions Chapter 6 Computational Engines 106 of 318 ChemBio3D 14 0 PerkinElmer For the Better Wave Function Selects closed or open shell See Specifying electronic configuration on page 272 for more details Polarization Specifies a polarization function for heavy atoms P S or heavier H If you have selected a Polarization function choose an H function Diffuse Adds a diffuse function to the basis set If you use a diffuse function specify Tight Convergence on the Advanced tab See the Gaussian manual for details The Advanced tab displays parameters that are adjusted less often Only those parameters that are applicable to the job type you have selected are active For minimizations the applicable parameters are Solvation Model Selects a solvation model See the SCRF keyword in the Gaussian manual for information on methods Solvent If you select a solvation model you may select a solvent The default solvent for all models is water Force Constants Options are a Nocalculation a Init
275. more than one structure each structure is defined as a fragment that has bonds and atoms as its child objects Every object has a set of properties including a property that defines whether or not it belongs to a parent object You can use the model explorer to group objects together and assign properties to them Grouped objects do not have to be contiguous objects in your model or even be part of the same structure For more information see Groups Note To display the Model Explorer Go to View gt Model Explorer The default setting all properties for an object is inherited from its parent This means that the parent determines the properties of its child objects until you change a property By changing properties of a child object you can visualize the part of the model you want to study You can use the model explorer to Define objects Add objects to groups Rename objects Delete objects with or without their contents Each type of object that can appear in the model explorer is described below Atoms Each atom object in the model explorer represents one atom in your model Atoms cannot be moved outside the frag ment that contains it If you deleted an atom from a fragment or a group within a fragment the model itself is changed Bonds Bond objects do not appear by default in the model explorer To display bonds go to File gt Preferences In the GUI tab select Show Bonds Fragments Each structure displayed in t
276. mparison of the steric energy components for cis 2 butene and trans 2 butene stretch bend non 1 4 van der 0 0193 0 3794 Waals 1 4 van der Waals 1 1742 1 1621 dipole dipole 0 0767 0 1032 total 0 137 1 5512 Chapter 6 Computational Engines 90 of 318 ChemBio3D 14 0 PerkinE For the Better The significant differences between the steric energy terms for cis and trans 2 butene are in the bend and Non 1 4 van der Waals steric energy terms The bend term is much higher in cis 2 butene because the C 1 C 2 C 3 and the C 2 C 3 C 4 bond angles must be deformed from their optimal value of 122 0 to 127 4 to relieve some of the steric crowding from the interaction of hydrogens on C 1 and C 4 The interaction of hydrogens on C 1 and C 4 of trans 2 butene is much less intense thus the C 1 C 2 C 3 and the C 2 C 3 C 4 bond angles have values of 123 9 much closer to the optimal value of 122 0 The Bend and Non 1 4 van der Waals terms for trans 2 butene are smaller there fore trans 2 butene has a lower steric energy than cis 2 butene Calculating multiple properties The Property Picker lets you compute multiple chemical topological and thermodynamic properties using multiple calculation engines For information on specific properties that you can calculate see Chemical properties on page 189 To apply the property picker 1 Go to Calculations gt Compute Properties The Property Picker dialog box appears In this d
277. n of the force field for bonds in 3 membered rings 4 Membered Ring Angles Bond angles for bonds in 4 membered rings In force field analysis angle bending portion of the force field for bonds in 4 membered rings 4 Membered Ring Torsionals The portion of the force field for the torsional angles in your model for atoms in 4 membered rings Angle Bending Parameters Standard bond angles In force field analysis the angle bending portion of the force field for bonds Bond Stretching Parameters Standard bond lengths In force field analysis bond stretching and electrostatic por tions of force field for bonds ChemBio3D Building Atom Types Building types available for building models Conjugated Pisystem Atoms Bond lengths for bonds involved in pi systems Pi system portion of the force field for pi atoms Conjugated Pisystem Bonds Pi system portion of the force field for pi bonds Electronegativity Adjustments Adjusts optimal bond length between two atoms when one atom is attached to an atom that is electronegative Elements Contains elements available for building models MM2 Atom Type Parameters van der Waals parameters for computing force field for each atom MM2 Atom Types Atom types in the model that may be used for MM2 calculations MM2 Constants Constants used for computing MM2 force field Out of Plane Bending Parameters Parameters to ensure atoms in trigonal planar geometry remain planar In force field analysis parame
278. n on page 272 From the Diffuse list select the diffuse function to add to the basis set 4 5 Set the Polarization functions If you select a function for Heavy Atom also select an H option 6 Select a Spin Multiplicity value 7 Select a Net Charge value Setting output options Use the General tab to set options for display and recording results of calculations To set the job type options 1 Inthe Minimize Energy dialog box click the Job Type tab 2 Select the appropriate options Display Every Iteration Watch the minimization process at each iteration in the calculation Displaying or recording each iteration increases the time to minimize the structure Send output to notepad Store the output in a notepad file at the specified location Kill temporary files Generate only the output file in CS GAMESS interface folder and do not generate the input file Send Back Output Display output in the comments box Average Equivalent Hydrogens Aggregate identical protons Specifying properties to compute You can specify which properties are computed The default Population Analysis type is Mulliken To specify properties 1 Inthe Minimize Energy dialog box click Properties 2 On the Properties tab set these options Select the properties to calculate Select the Population Analysis type Specifying the general settings Use the General tab to customize the calculation to the model To set the General settings 1
279. n the results are stored in an ARC file in the MOPAC Interface subfolder in your My Documents folder To create a structure from the ARC file Chapter 6 Computational Engines 132 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 1 Open the ARC file in a text editor 2 Delete the text above the keywords section of the file as shown in this illustration SUHMARY OF Alt CALCULATION HOPAC2000 Version 1 11 EMPIRICAL FORMULA C2 H 2000 7 5 SCF MNOK GEO OK ANT MULLIK ISCF VAS SPECIFIED SO OFGS WAS NOT USED SCF FIELD WAS ACHIEVED 17 187989 KCAL 71 89346 KJ 029 360221 EU 590 227818 CU 0 00000 DFBYE SYMMETRY 03a 7 11 8647014 CU 11 847 8 187 HEAT OF FORNATION ELECTRONIC EMERLY CORE CORE REPULSION DIPOLE NO OF FILLED LEVELS IONIZATION POTENTIAL HONO LUMO ENERGIES EU HOLECULAR WEICHT 30 069 SCF CALCULATIONS 1 COMPUTATION TIME 0 03 SECONDS A FINAL GEOMETRY OBTAINED SCF HHOK CEO OK ANT NULLIK 0 009000 800000 0 000000 1 523010 A0AONN 0 000000 B 1 112976 998169 0 000000 1 112976 998169 120 075691 1 112976 998169 120 0755691 1 112976 998169 179 99963 1 112976 998169 59 923813 1 112976 998169 59 923813 Pe E LEASES SES eee eeee ARC File A Delete text through this line B Keyword section 3 Save the file with a MOP extension 4 Open the MOP file CS GAMESS The General Atomic and Molecular Electronic Structure System CS GAMESS is a general ab initio quantum c
280. n below shows the distances between atom pairs at the completion of the alignment computation The distances in the Actual cell are close to the distances in the Optimal cell Measurement Actual A Optimal A v C 6 C 98 6 1484 5 0000 va C 1 C 93 6 0991 5 0000 v C 12 C 104 5 1307 5 0000 v C 16 C 108 4 6254 5 0000 v C 22 C 114 4 3976 5 0000 v C 28 C 1 20 4 1512 5 0000 v C 34 C 1 26 4 7687 5 0000 v C 41 C 133 5 1487 5 0000 v C 137 C 45 5 4206 5 0000 C 50 C 142 6 0719 5 0000 Figure 17 20 Measurements for docked polymers Your results may not match those described here The relative position of the two fragments or molecules at the start of the docking computation can affect results For more accurate results lower the minimum RMS gradient Tutorial 8 Viewing Orbitals The highest occupied molecular orbitals HOMO and lowest unoccupied molecular orbitals LUMO are commonly the most important orbitals affecting molecular reactivity This tutorial examines the orbitals of double bonds by look ing at ethylene the simplest molecule containing a double bond 1 Go to File gt New 2 Build a model of ethene 3 Go to Calculations gt Extended Huckel gt Calculate Surfaces The Highest Occupied Molecular Orbital HOMO is displayed by default To view the HOMO 1 Go to Surfaces gt Choose Surface gt Molecular Orbital 2 Go to Surfaces gt Select Molecular Orbital to see the HOMO L
281. nalysis is complete Compare the steric energies of cis and trans 2 butene To build trans 2 butene and compute properties 1 Go to File gt New 2 Select the Build from Text tool 3 Click in the model window A text box appears 4 Type trans 2 butene and press ENTER A molecule of trans 2 butene appears in the model window 5 Go to Calculations gt MM2 gt Compute Properties The Compute Properties dialog box appears 6 Click Run When the steric energy calculation is complete the individual steric energy terms and the total steric energy appear in the Output window Use the Output window scroll bar to view all of the output The units are kcal mol for all terms At the beginning of the computation the first message indicates that the parameters are of Quality 4 which means that the results are experimentally determined and verified _ Note The energy values are approximate and can vary slightly based on the type of processor used to calculate them These values appear a Stretch represents the energy associated with distorting bonds from their optimal length a Bend represents the energy associated with deforming bond angles from their optimal values a Stretch Bend term represents the energy required to stretch the two bonds involved in a bond angle when that bond angle is severely compressed a Torsion term represents the energy associated with deforming torsional angles in the molecule from their ideal val ues Chapte
282. nate and Bibliographic Entry Format Description ROSDAL Files RDL The ROSDAL Structure Language RDL file format is defined in Appendix C ROSDAL Syntax of the MOLKICK User s Manual and in this manual in File Formats on page 224 The ROSDAL format is primarily used for query searching in the Beilstein Online Database ChemBio3D supports the ROSDAL file format for export only Standard Molecular Data SMD Use the Standard Molecular Data SMD file format for interfacing with the STN Express application for online chem ical database searching Both import and export are supported SYBYL files Use the SYBYL SML SM2 ML2 file formats to interface with Tripos s SYBYL applications The SML and SM2 formats can be used for both import and export the ML2 format is supported for import only Job description file formats You can use Job description files to save customized default settings for calculations You can save customized cal culations as a Job Description file JDF or Job Description Stationery JDT Saving either format ina Chem3D job folder adds it to the appropriate Chem3D menu JDF files The JDF file format is a file format for saving job descriptions When you open a JDF file you can edit and save the settings JDT files The JDT file format is a template format for saving settings that can be applied to future calculations You can edit the settings of a template file however you cannot save your changes
283. nd appears in a new model window ACX files To download an ACX file using its ACX number 1 Go to Online gt Find Structure from ACX Number A dialog box opens 2 Inthe dialog box either enter the ACX number for the structure in the ACX No drop down list or select it from the list 3 To enter a location to save the file select Save As to navigate to the save location 4 Click Get File The file is downloaded and appears in a new model window To download an ACX file using a structure name 1 Go to Online gt Find Structure from Name at ChemACX com A dialog box opens 2 Inthe dialog box either enter the structure name in the Name drop down list or select it from the list 3 To enter a location to save the file select Save As to navigate to the save location 4 Click Get File The file is downloaded and appears in a new model window Ordering from ChemACX You can order chemicals through ChemACX from the ChemBio3D main menu _ Note To order chemicals you must have the ChemDraw ActiveX control installed To order a chemical Chapter 3 Basic Model Building 32 of 318 pP PerkinE or For the Better ChemBio3D 14 0 1 With a model in the model window go to Online gt Find Suppliers on ChemACX com 2 Install the ChemDraw ActiveX control if prompted Note You should be registered and or logged in to the PerkinElmer Web site before proceeding with the following steps The ChemACX Database Web site opens in a browse
284. nd close your model Go to File gt Save Select a directory in which to save the file Type tut2 in the text box at the bottom of the dialog box Click Save Click the model window to activate it oon A U Na Go to File gt Close Window Tutorial 3 Building models with Text This tutorial illustrates alternative methods for building models using the Build from Text tool Build From Name Using the Build from Text tool you can build a model by specifying its compound name To build the model 1 Select the Build from Text tool in the Building toolbar 2 Click anywhere in the model area 3 Enter the compound name for example cyclohexane in the text box that appears 4 Press ENTER The model appears in the model window Replacing Atoms Using the cyclohexane model change a hydrogen atom into a carbon atom 1 Click Build from Text tool 2 Click any hydrogen atom A text box appears 3 Type uppercase C and press ENTER The hydrogen changes to a carbon _ Note Element symbols and substructure names are case sensitive You must type an uppercase C to create a carbon atom If rectification is turned on the carbon valence is saturated with hydrogens See Rectifying atoms on page 27 You don t have to select the Text tool to use it Double clicking with the Move Objects tool has the same effect as single clicking with the Text tool For example replace two more hydrogens using this method 1 Select
285. nd in files of the format described by the file format All names must be unique The records in the table window are sorted by name Note While names are similar to atom type numbers they do not have to correspond to the atom type numbers of atom types In some cases however they do correspond Description The second field contains a description of the atom type such as C Alkane This description is included for your ref erence only The remaining fields contain information corresponding to the information in an Atom Types table Native formats There are three file formats that are native to ChemBio3D Unless you plan to use a model in another application you will want to save it in one of the native formats Chem3D XM Compatible with ChemBio3D version 9 0 or later Chem3D 8 0 Compatible with Chem3D versions 4 0 to 8 0 Chem3D 3 2 Compatible with Chem3D version 3 2 or earlier File format examples The following sections provide examples of the files created when you save ChemBio3D files using the provided file formats Alchemy file The sample Alchemy file Alchemy below was created using ChemBio3D for a model of cyclohexanol The numbers in the first column are line numbers that are added for reference only Chapter 14 File Formats 224 of 318 hemBio3D 14 I ne i i PerkinElmer For the Better 1 19 ATOMS 19 BONDS 1 C3 1 1236 c3 0 26 c3 LOL RI 1 838 g3 9934 c3 2815 1621 4448 8497 0275 6239
286. ne 75 is a header that indicates the End of File FORTRAN formats The FORTRAN format for each record of the Molecular Simulations MolFile format is as fol lows 1 1X A 3 atom list field value 1X 1 3F9 3 1X 1 F4 1 7 1X 1 1X A 1 8 1X 1 ESA J 1 4 1X 1 F9 3 4 2X 1 1X A1 bond list field values 2 1X l MOPAC ChemBio3D uses the MOPAC Data File format This format is described on pages 1 5 through 1 7 in the Description of MOPAC section and page 3 5 in the Geometry Specification section in the MOPAC Manual fifth edition For fur ther details about the MOPAC Data File format please refer to the above publication The table below is asample MOPAC output file from ChemBio3D for cyclohexanol MyCyclohexanolModel mop 0 00000 0 00100 1 00210 i 55 6959 1 1 2 3 1 55 31121 412 1 5703175 1321 1 172 662 112 3 Chapter 14 File Formats 241 of 318 ChemBio3D 14 0 PerkinElmer For the Better 07 8685 62 06751 10 0751 SET LT 09 4526 65 43868 09 9597 178 6209 09 5453 63 9507 09 4316 66 0209 110 549 176 0838 109 93 178 296 109 4596 64 43501 110 0104 178 325 4 109 6082 64 09581 H 0 94199 106 898 The following illustrates the components of the MOPAC Output File from ChemBio3D for C 1 Through C 4 of Cyc lohexanol A B G D E F G H a M vv 0 OM ct c 0 0 o 0 0 00 0 0 o ci C 1 54152
287. ne is a binding site in which all ligand atoms in the pose must be positioned outside the group radius An inclusion zone is a binding site in which at least one ligand atom in the pose must be positioned inside the group radius Each named group generates a new column in the final docking table in ChemBio3D with the name of the named group as the column heading This table has one row per pose A value of true is displayed if the pose obeys the inclusion or exclusion rule defined with the named group To define a group Inthe receptor model select up to 10 atoms to designate as a named group for the ligand Inthe AutoDock Interface select the Define Groups tab Click Add New Group From Selected Atoms Each new group you create appears in a list in the dialog box Inthe list in the dialog box enter a Group Name for the group oan A OO N gt Enter a binding Radius for the group The default is 3 5 Angstroms This is implemented by placing a sphere of the given radius around each atom in the named group O Select whether AutoDock should consider the group as either an Exclusion Zone or an Inclusion Zone 7 Optional Repeat the steps above to define more groups After you define your groups you use them to prepare the cavity for docking Step 4 Preparing the cavity prepare GPF The cavity is the empty space inside the receptor into which the small molecules will bind It is necessary to define the cavity to direct
288. nergy required to deform a bond angle described by three atoms The larger the KB value the more difficult it is to compress or stretch that bond angle XR2 This field contains the optimal value of a bond angle where the central atom of that bond angle is not bonded to any hydrogen atoms X represents the central atom of a bond angle and R represents the non hydrogen atom bon ded to X For example the optimal value of the 1 1 3 angle type for 2 2 dichloropropionic acid is the XR2 bond angle of 107 8 since the central carbon C 2 has no attached hydrogen atoms The optimal value of the 1 8 1 angle type for N N N triethylamine is the XR2 bond angle of 107 7 because the cent ral nitrogen has no attached hydrogen atoms Notice that the central nitrogen has a trigonal pyramidal geometry thus one of the attached non hydrogen atoms is a lone pair the other non hydrogen atom is a carbon XRH The XRH field contains the optimal value of a bond angle where the central atom of that bond angle is bon ded to one hydrogen atom and one non hydrogen atom X represents the central atom of a bond angle and R rep resents the non hydrogen atom bonded to X and H represents a hydrogen atom bonded to X For example the optimal value of the 1 1 3 angle type for 2 chloropropionic acid is the XRH bond angle of 109 9 since the central carbon C 2 has one attached hydrogen atom The optimal value of the 1 8 1 angle type for N N Chapter 7 P
289. ng Chapter 3 Basic Model Building 14 of 318 ChemBio3D 14 0 PerkinE aig For the Better Click Single and select a bond type Click Double and select a bond type a Click Triple and select Plain 5 Click in the ChemBio3D window to complete the action F Note To break a bond right click the bond and select Break Bond Creating rings To create a ring using the bond tools 1 Select a bond tool 2 Click drag from one atom in a structure to a nonadjacent atom in the same structure _ Note In general this will lead to distorted structures and MM2 or MMFF94 minimization will be needed to fix this Using the ChemDraw panel Using the ChemDraw panel you can draw two dimensional structures in the same way as you would in ChemBioDraw Alternatively you can build models with text using the Chem SMILES box of the ChemDraw panel As you draw your structure the corresponding 3D model appears in the Model window To build a model using the ChemDraw panel 1 Goto View gt ChemDraw Panel The ChemDraw panel appears 2 Click in the panel to activate it The Tools palette appears g Note If you don t see the Tools palette right click in the ChemDraw panel and select View gt Show Main Toolbar 3 Select a tool in the Tools palette and click in the ChemDraw panel to draw structure using the selected tool With the ChemDraw panel LiveLink option selected in the upper left corner of the ChemDraw panel the corresponding 3D mode
290. ng atom and the first angle defining atom All angles are meas ured in degrees 5 Beginning with line 5 the serial number of a second angle defining atom and a second defining angle follows the first angle Finally anumber is given that indicates the type of the second angle If the second angle type is zero the second angle is a dihedral angle New Atom Distance defining Atom First Angle defining Atom Second Angle defining Atom Otherwise the third angle is a bond angle New Atom Distance defining Atom Second Angle defining Atom If the second angle type is 1 then the new atom is defined using a Pro R Pro S relationship to the three defining atoms if the second angle type is 1 the relationship is Pro S f Note You cannot position an atom in terms of a later positioned atom The following is a sample of an Internal coordinates output file for cyclohexanol created in ChemBio3D al 111 54146 1 2 1 53525 1 111 7729 11 1 53967 2 109 7132 3 55 6959 0 Chapter 14 File Formats 229 of 318 ChemBio3D 14 0 PerkinElmer For the Better 939921 111 703 2 993172 H 209419 2 1107535 1 57 0318 0 40195 2 107 6989 3 172 6532 0 742 2 09 39 4 629 1 109 4 568 1 74 664 2 606 2 542 1 493 1 664 4 617 4 664 3 109 606 3 09 4 942 1 106 8998 2 Bonds Bonds are indicated in Internal coordinates files in two ways First a bond is automatically created between each atom except the O
291. ngs gt Model Display tab and select or deselect Show Delocalized Bonds as Dashed Lines Setting selection color Selected atoms and bonds are highlighted in yellow color by default You can change the default selection color in the Model Settings dialog box 1 Go to File gt Model Settings The Model Settings dialog box appears Chapter 3 Basic Model Building 20 of 318 ChemBio3D 14 0 Perkin For the Better 2 Click the Color amp Fonts tab 3 Select the desired color from the Selection Color drop down list 4 Click OK Adjusting bond width You can adjust the width of some or all bonds in your model To adjust the width of one or more selected bonds 1 Select one or more bonds 2 Right click the selected bond s 3 Choose Select Object Bond Size from the context menu The bond size slider appears 4 Move the slider to adjust the width 5 Optional To reset the bond to its default width right click the bond and select Reset to Default To adjust the width for all bonds in your model 1 Go to File gt Model Settings and select the Atom amp Bond tab 2 Move the Bond Size slider to the desired width 3 Click OK 4 Optional To reset all bonds to their default width go to File gt Model Settings Then select the Atom amp Bond tab and click Reset to Default Removing bonds and atoms To remove an atom or bond 1 Do one of the following to remove an atom or bond a Click the Eraser tool and click t
292. nics correction for amide bonds Use the additional keyword NOMM to tum this keyword off Electrostatic potential Electrostatic potential charge computation gives useful information about chemical reactivity The electrostatic poten tial is computed by creating an electrostatic potential grid ChemBio3D reports the point charges derived from the grid In general these atomic point charges give a better indication of likely sites of attack when compared to atomic charges derived from the Coulson density matrix Charges or Mulliken population analysis Mulliken Charges The Chapter 6 Computational Engines 117 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 uses for electrostatic potential derived charges are generally the same as for atomic charges For examples see Charges on page 117 There are two properties available for calculating atomic point charges Wang Ford Charges and Electrostatic Poten tial Wang Ford charges This computation of point charges can be used with the AM1 potential function only _ Note For elements not covered by the AM1 potential function use the Electrostatic Potential property Below are the keywords sent to CS MOPAC PMEP Sent to CS MOPAC to specify the generation of Point Charges from PMEP QPMEP Sent to CS MOPAC to specify the Wang Ford electrostatic Potential routine GEO OK Sent to CS MOPAC to override checking of the Z matrix MMOK Sent to CS MOPAC to specify Molecular Me
293. nless you are an expert user Before making changes to any parameters create a back up copy of the original parameter table and remove it from the C3D Items directory The elements The Elements table Elements xml contains the elements for building your models The fields that comprise the Ele ments table are listed below Symbol Normally you use only the first column of the Elements table while building models If you are not currently editing a text cell you can quickly move from one element to another by typing the first letter or letters of the element symbol Cov Rad The covalent radius is used to approximate bond lengths between atoms Pattern The pattern of the element Color The colors of elements are used when the Color by Element check box is selected in the control panel To change the color of an element double click the current color The Color Picker dialog box appears in which you can specify a new color for the element To use an element in a model type its symbol in the Replacement text box or paste it after copying the cell in the Symbol field to the Clipboard and press ENTER when an atom is selected or double click an atom If no atom is selected a fragment is added Atomic number The atomic number of the element Atomic numbers are not assigned to either Lone pair elections or generic atoms Deuterium has an atomic number of 1 2 Building types The Building Atom Types table Chem3D Building Atom Types
294. nload AutoDock and the AutoDock Tools you indicate where in your local drive you want to store the files You can move these files to another directory or download them again as needed You can also change where AutoDock stores the generated log files To configure AutoDock 1 If the AutoDock Interface is not open go to Calculations gt AutoDock Interface gt Setup AutoDock Calculation 2 Select the General tab 3 To change the AutoDock working folder click Change Directory under Working Directory This folder contains all the temporary files used in the current AutoDock run a Browse for a new folder to save the log files and click OK _ Note You will not be permitted to proceed with the calculation unless the working directory is empty of files You have to either choose another directory using Change Directory option or browse to the working directory and delete the files 4 Optional To change the AutoDock files folder click Change Directory under AutoDock This folder contains the AutoDock executable files This location should only be changed if the location of the AutoDock executable file changes a Browse for a new folder to save the AutoDock files and click OK 5 Optional To change the AutoDock Tool files folder click Change Directory under AutoDock Tools This folder contains the AutoDock tools executable files This location should only be changed if the location of the AutoDock tools executable file changes a Br
295. note the surface selected 2 On the Surfaces toolbar click Display Mode Lie and choose Translucent 3 On the Surfaces toolbar click Color Mapping ES and choose Spin Density 4 On the Surfaces toolbar choose Isocharge p The Isocharge tool appears Tsocharge 000 0 002 0 100 Figure 17 26 Using the Isocharge tool 5 Set the isocharge to 0 050 The number in the middle is the current setting _ Note The isocharge is used to generate the surface You can adjust this value to get the display you want The illustration below was made with the setting of 0 0050 Figure 17 27 Viewing the total charge density surface Chapter 17 Tutorials 309 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better Most of the surface is gray indicating that there is no contribution to it from unpaired electrons The areas of red centered over the terminal carbons is a visual representation of the expected delocalization of the radical there is some radical character simultaneously on both of these carbons Now toggle the surface off by clicking the Surfaces icon EAS Spin Density Here we determine the raw spin density alone not mapped onto the charge density surface 1 On the Surfaces toolbar point to Surface and select Total Spin Density 2 Go to Surfaces gt Display Mode gt Wire Mesh 3 Set Isospin to 0 001 Figure 17 28 Wire mesh surfaces There is a large concentration of unpaired spin
296. ntet To request the second excited state use the following set of keywords Second excited Singlet OPEN 2 2 ROOT 3 SINGLET Second excited triplet OPEN 2 2 ROOT 3 TRIPLET C l n where n 3 is the simplest case Second excited quintet OPEN 4 4 ROOT 3 QUINTET C l n where n 5 is the simplest case Excited State UHF Only the ground state of a given multiplicity can be calculated using UHF Odd electron systems Often anions cations or radicals are odd electron systems Normally the ground states and excited state con figuration can be doublet quartet or sextet Ground State RHF Doublet ground state This is the most common configuration No additional keywords are necessary Quartet Use the following keyword combination QUARTET OPEN 3 3 Sextet ground state Use the following keyword combination SEXTET OPEN 5 5 Ground State UHF For UHF computations all unpaired electrons are forced to be spin up alpha Doublet ground state This is the most common configuration for a odd electron molecule No additional keywords are necessary UHF will yield energies different from those obtained by the RHF method Quartet and Sextet ground state Use the keyword QUARTET or SEXTET Excited State RHF First Excited State The first excited state is actually the second lowest state the root 2 fora given spin system Doublet Quartet Sextet To request the first excited state use the following sets of keywords First excited doublet RO
297. o enter text instead of typing the text To use the Table editor to enter text Go to View gt Parameter Tables gt Chem3D Building Atom Types Select the element or building type in the table Press CTRL C Double click in the ChemBio3D Model Window In ChemBio3D go to Edit gt Paste Press ENTER Ooo A WN Building models from SMILES strings To build models from names using the Chem SMILES box do one of the following a n the Chem SMILES box enter a chemical name or a SMILES string and press ENTER Chapter 3 Basic Model Building 17 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Copy a name or SMILES string from a document paste it into the Chem SMILES box and press ENTER Tip You can paste aname or SMILES string into the Model window to draw a 3D model You can also paste chemical formulae into the ChemBio3D Model window Be aware however that a formula may represent an iso mer By default the ChemDraw panel replaces existing structures if you use the Chem SMILES box to draw structures To ensure that existing structures are not replaced while you draw structures using the Chem SMILES box click Add or Replace contents of ChemDraw panel tool Qe Adding fragments A model can comprise several fragments Typically a fragment consists of one structure in your model To add a fragment using the Build from Text tool 1 Click in an empty area of the window A text box appears 2 Type
298. o the shaded elements in the following table NalMa ai sif P s x ca 2n Ga Ge as se Br kr Rb sr Cd in Sn sb te 1 xe jes Haf ti Pb Bi Po at An The following apply to PM3 PM3 is areparameterization of AM1 Chapter 15 References 279 of 318 ChemBio3D 14 0 PerkinE For the Better a PM3 is a distinct improvement over AM1 a Hypervalent compounds are predicted with considerably improved accuracy a Overall errors in AH pare reduced by about 40 relative to AM1 a Little information exists regarding the limitations of PM3 This should be corrected naturally as results of PM3 cal culations are reported a The barrier to rotation in formamide is practically non existent In part this can be corrected by the use of the MMOK option For more information about MMOK see the online MOPAC Manual MNDO d applicability and limitations Modified Neglect of Differential Overlap with d Orbitals MND O d may be applied to the shaded elements in the table below ro fen nse cs Ba Hal Ti Pb Bi Po at frn MNDO d is a reformulation of MNDO with an extended basis set to include d orbitals This method may be applied to the elements shaded in the table below Results obtained from MNDO d are generally superior to those obtained from MNDO The MNDO method should be used where it is necessary to compare or repeat calculations previously per formed using MNDO The following types of calculations as
299. oer a at tsa Reig es ase ee oes tds a Ce aut Pa een ete dea eee 282 PerkinElmerIntonmatics 22 2 4 222222 22ce 2s eyo eee ed dda ds Sasol nce a eee so bn 2 oe aL calves ono dodge ec eee EAEri 282 Online documentation seses ocak te vee g soe locas ee eter Mia le eee ee ee le ee ee yee Sah oS ck 282 Online registration 000002 o ccc cee ee eee cece eee e bebe eee eee eeeeeeceeeeeeecccseeceeeceeeeees 282 ChemOffice SDK 1 2 00 2 c cece ee eee cece cece eee c cece eee e cece cee ee cee eeeeceeeceeeseeeeeeeseeeeeseeneees 282 Troubleshooting 20 00 2 e cece eee e eee cece eee cece cece cece cece cece eeeeeeeeeeeeeeeeeeees 282 Chapter 17 Tutorials 0 0000000000000 0000000000000000 eee ccccce eee cece cece cence eeeeecceeeeeeeeeeees 284 Building models 1 22 2 22 2 e cece eee cece cece cece eee c cece cece cee cece cece cece EDE EDEA aa oaoa oarra anan 284 Table of Contents vi ChemBio3D 14 0 PerkinElmer For the Better Examining models 22 2 ue cecocnates d custt adpan eee eaa e eda ee e ee eei aaoi 296 Using calculation engines 000000000000000 0000000000000000 cee ee cece cece eee eeeeeeeeeeeeeeeeeeeeeeeeeeeees 312 Table of Contents vii hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better Recent Additions ChemBio3D introduces a variety of improvements not found in earlier versions These are briefly described below Microsoft Office 2013 and Windows 8 1 ChemBio3D is compatible with Microsoft
300. of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Figure 17 6 Model of ethylene Building Cyclic Compounds You can continue building on the ethylene model to create cyclohexane First change ethylene back to ethane 1 Click the Select tool in the Building toolbar 2 Right click the double bond 3 Inthe context menu go to Set Bond Order gt Single Hiding Hydrogens Sometimes you may want to hide the hydrogen atoms in your model to make building easier The hydrogens are still there and chemically active they are just not in view To hide the hydrogens go to View gt Model Display gt Show Hydrogen Atoms gt Hide Adding atoms Here we add more atoms to the model to create a cyclohexane ring 1 Click the Single Bond tool in the Building toolbar 2 Drag downward from the left carbon Another C C bond appears 3 Continue adding bonds until you have six carbons as shown below Chapter 17 Tutorials 289 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Create a ring 1 Drag from one terminal carbon across to the other 2 Release the mouse button to close the ring Chapter 17 Tutorials 290 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Figure 17 7 Building cyclohexane with the bond tool Serial Numbers and Labels Whenever you build or examine a model atoms of the same type all look the same as they should However it is sometimes convenient to distinguis
301. ole moment 1 Go to Calculations gt MOPAC Interface gt Minimize Energy 2 On the Theory tab choose AM1 3 On the Property tab select Polarizabilities 4 Click Run The following table is a subset of the results showing the effect of an applied electric field on the first order polar izability for m nitrotoluene 0 000000 108 23400 97 70127 18 82380 0 250000 108 40480 97 82726 18 83561 0 500000 108 91847 98 20891 18 86943 Chapter 6 Computational Engines 124 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 The table below contains the keywords sent to CS MOPAC and those you can use to affect this property POLAR E n1 n2 n3 Sent to CS MOPAC to specify the polarizablity routine nis the starting voltage in eV The default value is E 1 0 You can reenter the keyword and another value for n to change the starting voltage Sent to CS MOPAC to override checking of the Z matrix Sent to CS MOPAC to specify Molecular Mech anics correction for amide bonds Use the additional keyword NOMM to tum this keyword off Example 5 Phase stability In this example we compare the stability of the glycine Zwitterion in water and gas phases To compare stabilities 1 Go to File gt New 2 Click the Build from Text tool 3 Click in the model window A text box appears 4 Type HGlyOH and press ENTER A model of glycine appears Figure 6 8 Glycine model 5 Go to Calculations gt MOPAC Interfac
302. olynomial switching function Automatic pi system calculations when necessary Torsional and non bonded constraints ChemBio3D stores the parameters for the potential energy function in parameter tables To view the tables go to View gt Parameter Tables and select one of the MM2 tables Each parameter is classified by a Quality number which indicates the reliability of the data The quality ranges from 4 where the data is derived completely from experimental data or ab initio data to 1 where the data is guessed by ChemBio3D Chapter 9 Computation Concepts 172 of 318 ChemBio3D 14 0 Perkin For the Better The parameter table MM2 Constants contains adjustable parameters that correct for failings of the potential functions in outlying situations Caution Editing of MM2 parameters should only be done with the greatest of caution by expert users Within a force field equation parameters operate interdependently changing one normally requires that others be changed to compensate for its effects Bond stretching energy The bond stretching energy equation is based on Hooke s law E stretch 71 94 DK r Bonds The parameters are stored in the Bond Stretching parameter table Unique K and P parameters are assigned to each pair of bonded atoms based on their atom types C C C H O C The K parameter controls the stiffness of the spring s stretching bond stretching force constant r defines its equilibrium length the st
303. om Text tool Click in the model window A text box appears Type EtH and press ENTER Click the Select tool Select H 8 7 Press BACKSPACE to remove the H 8 hydrogen oa A OO N If automatic rectification is on a message appears asking to turn it off to perform this operation 8 Click Turn Off Automatic Rectification The Ethyl Radical is displayed Figure 6 10 Ethyl radical model To perform the HFC computation 1 Go to Calculations gt MOPAC Interface gt Minimize Energy 2 On the Job amp Theory tab choose the PM3 potential function and the Open Shell Unrestricted wave function 3 On the Properties tab choose Hyperfine Coupling Constants 4 Click Run This table lists the hyperfine coupling constants Chapter 6 Computational Engines 127 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Example 7 UHF spin density Again using the ethyl radical calculate the UHF spin density 1 Create the ethyl radical as described in Spin density on page 120 2 Go to Calculations gt MOPAC Interface gt Minimize Energy 3 On the Theory tab select PM3 4 On the Properties tab select Open Shell Unrestricted and Spin Density 5 Click Run The Message window displays a list of atomic orbital spin densities The atomic orbitals are not labeled for each value however the general rule is shown in the table below CS MOPAC only uses s Py Py and P orbitals Chapter 6 Computat
304. omatic keywords The following contains keywords automatically sent to MOPAC and some additional keywords you can use to affect convergence EF Automatically sent to MOPAC to specify the use of the Eigenvector Following EF minimizer BFGS Prevents the automatic insertion of EF and restores the BFGS minimizer GEO OK Automatically sent to MOPAC to override checking of the Z matrix MMOK Automatically sent to MOPAC to specify Molecular Mechanics correction for amide bonds Use the addi tional keyword NOMM to turn this keyword off RMAX n nn The calculated predicted energy change must be less than n nn The default is 4 0 RMIN n nn The calculated predicted energy change must be more than n n The default value is 0 000 PRECISE Runs the SCF calculations using a higher precision so that values do not fluctuate from run to run Overrides safety checks to make the job run faster RECALC 5 Use this keyword if the optimization has trouble con verging to a transition state For descriptions of error messages reported by MOPAC see the MOPAC manual Chapter 15 References 270 of 318 ChemBio3D 14 0 I x PerkinElmer For the Better Additional keywords Keywords that output the details of a particular computation are shown in the following table Terms marked with an asterisk appear in the out file ENPART All Energy Components FORCE Zero Point Energy FORCE Vibrational Frequencies Microstates used in MECI cal culat
305. on density in the space surrounding the nuclei of a molecule or the probability function for finding electrons in the space around a molecule The default isocharge value of 0 002 atomic units a u This value approximates the molecule s van der Waals radius and represents about 95 of the entire three dimen sional space occupied by the molecule The total charge density surface is the best visible representation of a molecule s shape as determined by its elec tronic distribution The total charge density surface is calculated from scratch for each molecule and is generally more accurate than the space filling display For total charge density surfaces the properties available for mapping are molecular orbital spin density electrostatic potential and partial charges The color scale uses red for the highest magnitude and blue for the lowest magnitude of the property Neutral is white Chapter 4 Displaying Models 68 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better Molecular orbitals Molecular Orbital MO surfaces visually represent the various stable electron distributions of a molecule According to frontier orbital theory the shapes and symmetries of the highest occupied and lowest unoccupied molecular orbit als HOMO and LUMO are crucial in predicting the reactivity of a species and the stereochemical and regiochemical outcome of a chemical reaction You can choose the orbital to map onto the surface with the Molecul
306. ond records is the bond type Finally the last line in the file is the Number of Features record which contains the number of feature records in the molecule ChemBio3D does not use this information FORTRAN formats The FORTRAN format for each record of the SYBYL MOL File format is as follows Line Description FORTRAN Format Number of Atom 14 1X MOL 20A2 11X s File Name 14 Atom records 214 3F9 4 2A2 Number of Bonds 14 1X MOL record Bond records 314 9X 14 Number of Features 14 1X MOL record SYBYL MOL2 file The SYBYL MOL2 file format SYBYL2 is a portable representation of aSYBYL molecule The file which is in ASCII format contains all the information necesary to construct the molecule The sample file shown below of cyc lohexanol was created using ChemBio3D Ultra SMALL USER_CHARGES lt TRIPOS gt ATOM ISYBYL is a product of TRIPOS Chapter 14 File Formats 252 of 318 ChemBio3D 14 0 8340 5916 8165 1138 8714 5366 1759 1512 3306 7044 9114 5439 4530 1863 0049 6002 2732 6114 2933 lt TRIPOS gt BOND 32126 3023 2202 1685 2582 1760 2616 3949 1849 2910 9670 4296 3535 2022 2529 1157 4072 9100 4198 Chapter 14 File Formats 0 9718 0 0 a I 0 0691 6525 2118 1708 4125 3768 8316 8930 4295 4722 1636 0880 5074
307. ons Out of plane bending The Out of Plane Bending table Out of Plane Bending Parameters xml contains parameters that ensure that atoms with trigonal planar geometry remain planar in MM2 calculations The table contains four fields Bond Type Force Con stant Quality and Reference Bond Type The first field is the Bond Type which is described by the atom type numbers of the two bonded atoms For example Bond Type 2 3 is a bond between an alkene carbon and a carbonyl carbon Force constant The force constant field or the out of plane bending constant field indicates the amount of energy required to cause a trigonal planar atom to become non planar The larger the value of the force constant for an atom the more difficult it is to coerce that atom to be non planar F Note Out of plane bending parameters are not symmetrical For example the force constant for a 2 3 bond refers to the plane about the type 2 atom The force constant for a 3 2 bond refers to the plane about the type 3 atom Qualty The quality of a parameter indicates the relative accuracy of the data Accuracy Level The parameter is an estimate by ChemBio3D See Estim ated parameters on page 139 The parameter is derived from experimental data The parameter is well confirmed The parameter is theorized but not confirmed Reference The reference for a measurement corresponds to a reference number in the References table References indicate where
308. or excluded Figure 4 16 Partial surface excluding solvent atoms After displaying a surface you can set surface transparency and reflectivity You can color the surface by atom ele ment or group color or by group hydrophobicity in addition to monochromatic surfaces of any color You can also restrict the surface either by distance from the selected group or by flooding Volume slicing The volume slicing tool lets you project almost any molecular surface into a 2D Plane After calculating the surface you can slice through your model in either the X Y or Z planes and adjust the location of the plane as desired 1 Calculate a desired surface For more information see Molecular surfaces on page 62 2 To display the surface go to Surface gt Choose Surface and select the surface to display _ Note The volume slicing tool cannot be applied to Connolly surfaces 3 Inthe Model Display toolbar select the volume slice button 3 The volume slicing dialog box appears The volume slicing dialog box includes three sliders that you use to control the locations of each plane in the model window 4 Inthe dialog box select one or more check boxes to display the planes you want to view 5 Move the sliders to adjust the location for each plane 6 To orient a plane so that it is facing you parallel with the screen click the corresponding button under Face User The button displays one side of the selected plane the button di
309. orm that is generating the file 14 Line 27 contains the header for the Atom Lists section 15 Line 28 contains a listing of all the possible fields for the atom list section When the file is created using Chem3D Pro the following fields are used Atom Lbl Type and x y z 16 Lines 29 47 each contains 28 fields describing information about each of the atoms in the structure the first field is the atom number 6 the second field is the atom label C the third field is the atom type 10 the fourth field and fifth fields contain 2D coordinates and contain zeros when the file is created using Chem3D Pro the sixth field is the X coordinate 0 113 and the fifth field is the Y coordinate 1 005 the sixth field is the Z coordinate 0 675 the seventh through fifteenth fields are ignored and contain zeros when the file is created by Chem3D Pro the six teenth field is again the atom label C the eighteenth field is again the atom number 6 the nineteenth field is the segment field the twentieth field is the coordination field the twenty first field is ignored the twenty second field is called the saturation field if the atom is attached to any single double or delocalized bonds this field is 1 not saturated otherwise this field is 0 The twenty third through the twenty sixth fields are ignored and contain zeros when the file is created using Chem3D Pro the twenty seventh field is again the atom label C Note Atom types in
310. ormation see Using keywords on page 269 Chapter 6 Computational Engines 112 of 318 ChemBio3D 14 0 Perkin For the Better Display Every Iter Displays the minimization at ation each iteration in the calculation Increases the time to minimize the structure Show Output in Note Sends the output to a text file pad Send Back Output Displays each measurement in the Output window Increases the time to minimize the structure Optimize to transition state To optimize your model to a transition state use a conformation that is as close to the transition state as possible Do not use a local or global minimum because the algorithm cannot effectively move the geometry from that starting point See also Example on page 114 To optimize a transition state 1 Go to Calculations gt MOPAC Interface gt Optimize to Transition State The CS MOPAC Interface dialog box appears 2 Onthe Job amp Theory tab select a Method and Wave Function F Note Unless you are an experienced CS MOPAC user use the Transition State defaults 3 On the Properties tab select the properties you wish to calculate from the final optimized conformation 4 On the General tab type any additional keywords to use 5 Click Run The information about the model and the keywords are sent to CS MOPAC If you have selected Send Back Output the Output window appears The Output window displays the status throughout the minimization The table be
311. ou use the clean up command the selected atoms are repositioned to reduce errors in bond lengths and bond angles Planar atoms are flattened and dihedral angles around double bonds are rotated to 0 or 180 degrees Also any bond lengths or bond angles you may have set in the measurements table are overridden ChemBio3D tries to adjust the structure so that its measurements match those in the Optimal column These optimal values are the standard measurements in the Bond Stretching and Angle Bending parameter tables For all other measurements per forming a Clean Up or MM2 computation alters these values To use values you set in these computations you must apply a constraint See Setting constraints on page 79 for information Copying and printing ChemBio3D offers several options for you to copy embed and print models The best option depends on your needs and preferences Copying You can copy ChemBio3D models into other applications such as a desktop publishing program How you copy the model depends how you want the model to appear in the new application When you copy a model from ChemBio3D into another application the model retains its properties If you want to edit the model you can only do it using ChemBio3D After you edit and save the structure the changes will be reflected in the application where you have pasted the model Copying as an editable model To copy a model 1 InChemBio3D select the model 2 Go to Edit gt Copy
312. ounds where another element might be substituted Dummy atoms are also useful for positioning atoms in a Z matrix to export to other applications for further analysis This is helpful when models become large and connectivities are difficult to specify f Note Dummy bonds and dummy atoms are ignored in all computations To add a dummy bond and dummy atom 1 Select the Dummy Bond tool 2 Point to an atom and drag from the atom A dummy bond and a dummy atom are added to the model The atom cre ated is labeled Du the ChemBio3D element symbol for dummy atoms To add only a dummy atom 1 Select an existing atom 2 Using the Build from Text tool click the selected atom A text box appears 3 Inthe text box type Du and press ENTER Figure 5 1 A Dummy atom Chapter 5 Building Advanced Models 73 of 318 ChemBio3D 14 0 PerkinE For the Better Substructures For large models you may consider using substructures rather than building models one atom at a time A sub structure is a defined group of atoms such as a ring system residue or another structural feature For example you can use the Benzyl substructure to add a benzene ring or COOH to add a carboxylic acid functional group All the sub structure definitions are stored in the Substructure parameters table For more information see Substructures table on page 143 Building models from substructures To copy paste a substructure to the model window 1 To open
313. output structure file contains the original structures without the salt component and the output salt file contains the salt components that were stripped along with a reference to the original structure See Example 008 script py _ Note This example uses a default set of salts that PerkinElmer provides However you can also define a cus tomized salt table that enables you to designate which chemicals are considered salts Useful References There are numerous resources available for learning Python and C NET Just a few of the many books and Web sites are listed below Books Python a Beginning Python From Novice to Professional by Magnus Lie Hetland a Dive into Python by Mark Pilgrim a Learning Python by Mark Lutz amp David Ascher This is a beginner intermediate learning manual and reference a Python in a Nutshell by Alex Martelli This book is a brief introduction and good reference to Python C NET a C ina Nutshell by Peter Drayton Ben Albahari and Ted Neward a Pro C with NET 3 0 by Andrew Troelsen a C Essentials by Ben Albahari Peter Drayton and Brad Merrill a C 3 0 Cookbook by Jay Hilyard and Stephen Teilhet Web Sites Python You can find more information on Python at http www python org This is the official Python programming language site NET For information on NET see http msdn microsoft com Chapter 10 ChemScript 188 of 318 ChemBio3D 14 0 Chemical properties pP
314. over each of the terminal carbons and a small concentration over the central hydrogen This small amount of spin density is not very significant you could not even see it when looking at the mapped display earlier but the calculations show that it is in fact there Tutorial 10 Partial Charges Each atom of a molecule contributes an integral charge to the molecule as a whole This integral contribution is known as the formal charge of the atom To compute the integral charge of a molecule the number of electrons contributed by each of its atoms can be sub tracted from the number of protons in the nucleus of each of its atoms In ChemBio3D some atoms have non integral delocalized charges For example the two oxygen atoms in nitroben zene each have charges of 0 5 because there is one electron shared across the two N O bonds For more accuracy quantum mechanics calculations can produce partial charges which are also non integral However as shown in Tutorial 9 electrons in molecules actually occupy areas of the molecule that are not associated with individual atoms and can also be attracted to different atomic nucleii as they move across different atomic orbit als In fact bonds are a representation of the movement of these electrons between different atomic nucleii Because electrons do not occupy the orbitals of a single atom in a molecule the actual charge of each atom is not integral but is based on the average number of electrons in
315. owse for a new folder to save the AutoDock Tools files and click OK 6 Optional To install AutoDock a Inthe AutoDock dialog box click Download AutoDock The AutoDock download instructions appear ina Web browser b Download and install the latest version of AutoDock to your local hard drive c Inthe AutoDock dialog box click Set AutoDock Directory to select the path to where you installed AutoDock 7 Optional To install the AutoDock Tools a Inthe AutoDock dialog box click Download AutoDock Tools The AutoDock Tools download instructions appear in a Web browser b Download and install AutoDock to your local hard drive c Inthe AutoDock dialog box click Set AutoDockTools Directory to select the path to where you installed the AutoDock Tools Chapter 8 Docking 156 of 318 ChemBio3D 14 0 PerkinE aig For the Better Working with the AutoDock Interface The AutoDock Interface in ChemBio3D helps you perform the docking calculation Preparing an AutoDock calculation involves several steps each of which have been abstracted into a tab based dialog in the AutoDock Interface Following are the different steps involved in the docking calculation 1 Preparing receptor In this step you define the receptor The receptor may be either in a file or a model that is already open in ChemBio3D 2 Preparing ligand In this step you define one or more ligand to dock to the receptor The ligands may be either in a file or a model th
316. pe Attribute Shape Coefficient Sum of Degrees Sum of Valence Degrees T Topological Diameter Total Connectivity Total Valence Connectivity 216 of 318 ChemBio3D 14 0 Formal Charge G Gibbs Free Energy ChemBioDraw properties m z N Num Rotatable Bonds oO Ovality pP PerkinElmer For the Better vV Vapor Pressure WwW Water Solubility Wiener Index The properties listed below can be calculated in ChemBioDraw Ultra for ChemBioOffice 2014 For more information on these properties and how to calculate them see the ChemBioDraw online help B Boiling Point c Critical Pressure Critical Temperature Critical Volume CLogP CMR G Gibbs Free Energy ChemDraw Excel properties H Heat of Formation Henry s Law Constant L LogP LogS M Melting Point MR pKa tPSA The properties listed below can be calculated in ChemDraw Excel for ChemBioOffice 2014 For more information on these properties and how to calculate them see the ChemDraw Excel online help B Balaban index Boiling point c Cluster count Critical Pressure Critical Temperature Critical Volume Connolly Molecular Surface Area Connolly Solvent Accessible Surface Area Connolly Solvent Excluded Volume G Gibbs Free Energy H Heat of Formation Chapter 11 Chemical properties I Ideal Gas Thermal Capacity L LogP M Molar Refractivity N Number of rotatable bonds o Ovality P Principal Moments of In
317. provides these methods extended Huckel ChemBio3D 14 0 MOPAC Semi empirical other semi empirical methods AM1 MINDO 3 PMB etc Ab initio RHF UHF MP2 etc Gaussian CS GAMESS Figure 9 1 Computational Chemistry Methods Gaussian Molecular mechanical methods MM2 directly Chapter 9 Computation Concepts 164 of 318 ChemBio3D 14 0 PerkinE For the Better a Semi empirical Extended H ckel MINDO 3 MNDO MNDO d AM1 and PM3 methods through ChemBio3D and Gaussian a Ab initio methods through the ChemBio3D Gaussian or CS GAMESS interface Uses of computational methods Computational methods calculate the Potential Energy Surfaces PES of molecules The potential energy surface is the embodiment of the forces of interaction among atoms in a molecule From the PES structural and chemical information about a molecule can be derived The methods differ in the way the surface is calculated and in the molecular properties derived from the energy surface The methods perform the following basic types of calculations a Single point energy calculation The energy of a given geometry of the atoms in a model which is the value of the PES at that point a Geometry optimization A systematic modification of the atomic coordinates of a model resulting in a geometry where the forces on each atom in the structure is zero A 3 dimensional arrangement of atoms in the model rep resenting a local energy minimum a stable mol
318. pter 5 Building Advanced Models 85 of 318 ChemBio3D 14 0 PerkinElmer For the Better Figure 5 7 Enantiomer produced by reflection Building with Cartesian tables The Cartesian table displays the coordinates of each atom in your model relative to the model axes origin One way to build a new model is to paste Cartesian coordinates from a spreadsheet or some other table into an empty ChemBio3D Cartesian table After you paste the data ChemBio3D applies minimization parameters and atom types to determine the structure of the model To copy Cartesian Z matrix coordinates into ChemBio3D 1 Select the table in the text or spreadsheet file 2 Press CTRL C to transfer data to the clipboard 3 Go to View gt Cartesian Table The table opens 4 Right click in a blank Cartesian table and select Paste Example 1 chloroethane Cartesian table space character as separator C 0 0 464725 0 336544 0 003670 C 0 0 458798 0 874491 0 003670 Cl 0 0 504272 1 818951 0 003670 O 1 116930 0 311844 0 927304 0 1 122113 0 311648 0 927304 O 0 146866 1 818951 0 003670 0 1 116883 0 859095 0 923326 0 1 122113 0 858973 0 923295 coos Example 2 ethane Cartesian table tab as separator 0 4956 0 5782 0 0037 0 4956 0 5782 0 0037 0 0552 1 5557 0 0037 l 1517 0 5252 0 9233 1 1569 0 5248 0 9233 0 0552 1 5557 0 0037 11517 0 5252 0 9233 1 1569 0 5248 0 9233 ToT ete eaa Example 3 ethenol Z Matrix table tab as separa
319. ptor in energetically favorable orientations For example you can explore possible conformers of a drug candidate to determine whether it can attach to a binding site in a selected protein ChemBio3D maintains an interface to AutoDock to perform the docking calculation AutoDock starts with a random population of poses of the ligand A pose is an instance of the ligand at a given orientation location and conformation AutoDock selects the best poses from the population and discards the rest From the selection AutoDock develops new poses to rebuild the population using a genetic algorithm Each selection rebuilding cycle is a generation AutoDock repeats the cycle for a maximum number of generations that you define From the final generation AutoDock retrieves the best poses and reports them as the final calculation results 7 Note AutoDock functions generate a log file If AutoDock reports an error refer to the log file to determine whether the error is the result of an AutoDock or a ChemBio3D function See Technical Support on page 1 Installing AutoDock Before using AutoDock you must install both AutoDock and AutoDockTools It is available from the AutoDock Web site as a free download You need to install it only once To install AutoDock 1 In ChemBio3D go to Calculations gt AutoDock Interface gt Install AutoDock AutoDock Tools 2 Inthe AutoDock dialog box click Download AutoDock The AutoDock Web site opens in a Web browser
320. r 6 Computational Engines 89 of 318 hemBio3D 14 I enemBios 9 PerkinElmer For the Better Non 1 4 van der Waals term represents the energy for the through space interaction between pairs of atoms that are separated by more than three atoms For example in trans 2 butene the Non 1 4 van der Waals energy term includes the energy for the interaction of a hydrogen atom bonded to C 1 with a hydrogen atom bonded to C 4 1 4 van der Waals represents the energy for the through space interaction of atoms separated by two atoms For example in trans 2 butene the 1 4 van der Waals energy term includes the energy for the interaction of a hydrogen atom bonded to C 1 with a hydrogen atom bonded to C 2 a The Dipole Dipole steric energy represents the energy associated with the interaction of bond dipoles For example in trans 2 butene the Dipole Dipole term includes the energy for the interaction of the two C Alkane C Alkene bond dipoles We can use a force field method to compare steric energy values in cis 2 butene to those in the trans isomer To build a cis 2 butene and compute properties 1 Go to Edit gt Clear to delete the model 2 Double click in the model window A text box appears 3 Type cis 2 butene and press ENTER A molecule of cis 2 butene appears in the model window 4 Go to Calculations gt MM2 gt Compute Properties The steric energy terms for cis 2 butene appears in the Output window 5 Click Run Below is a co
321. r and obtain the most up to date driver If you still have trouble contact us with the relevant details about the original driver and the resulting problem 3 Try reinstalling the software Before you reinstall uninstall the software and disable all background applications including screen savers and virus protection See the complete uninstall instructions on the Technical Support web page 4 If the problem still occurs use our online contact form and provide the details of the problem to Technical Support Chapter 16 Online Resources 283 of 318 ChemBio3D 14 0 PerkinElmer For the Better Tutorials This section provides examples of some basic tasks you can perform with ChemBio3D Building models Tutorial 1 Building Models in 2D on page 284 a Tutorial 2 Building with bond tools on page 285 a Tutorial 3 Building models with Text on page 292 Examining models a Tutorial 4 Examining Conformations on page 296 a Tutorial 5 The Dihedral Driver on page 299 Tutorial 6 Overlaying Models on page 301 Tutorial 7 Aligning Models on page 303 a Tutorial 8 Viewing Orbitals on page 306 a Tutorial 9 Mapping Surfaces on page 307 Tutorial 10 Partial Charges on page 310 Using calculation engines Tutorial 11 Rotamer Analysis on page 312 a Tutorial 12 Calculating Rotational Bonds on page 315 Before starting the tutorials we recommend that you choose the default settings and an appropriate di
322. r both Since ChemScript scripts are like any other Python scripts or NET program you can execute the scripts using either the Windows command line or any development environment Getting Started By default ChemScript and Python 3 2 are installed on your local computer when you install ChemBioOffice After the installation we suggest that you follow the simple exercises in this section to familiarize yourself with ChemScript For editing ChemScript files we recommend that you use one of the many programming tools that are available One of these tools IDLE is included with the Python installation To learn more about IDLE see the online Help in the IDLE main menu Starting IDLE From the Start menu go to All Programs gt Python 3 2 gt IDLE Python GUI After Python starts a Python shell opens in IDLE and the header indicates a version of Python Ex 3 2 and a version of IDLE Ex 1 2 A prompt will also appear gt gt gt Loading the ChemScript Library At the command prompt type the line below and press lt Enter gt import ChemScript14 Chapter 10 ChemScript 182 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better _ Note The command is case sensitive A Welcome to CS ChemScript message appears followed by a command prompt ChemScript Help You can read a description of any ChemScript class within IDLE For example enter the line below to return Help for the ChemScript Atom class help Ato
323. r segment comprising six repeat units of tetrafluoroethylene appears in the model window To perform the computation 1 Select C 2 the leftmost terminal carbon then SHIFT click C 33 the rightmost terminal carbon 2 Go to Structure gt Measurements gt Display Distance Measurement A measurement for the overall length of the molecule appears in the Measurement table 3 Go to Calculations gt MM2 gt Molecular Dynamics 4 Click Run When the calculation begins the Output Window appears Figure 6 2 C 2 C 33 distance before calculation The C 2 C 33 distance before the calculation is approximately 9 4A Chapter 6 Computational Engines 103 of 318 ChemBio3D 14 0 PerkinElmer For the Better 5 Scroll down to the bottom of the Output window and examine the C 2 C 33 distance for the molecule at 0 190 picoseconds Figure 6 3 C 2 C 33 distance after calculation The C 2 C 33 distance is approximately 13 7A 42 greater than the initial C 2 C 33 distance Gaussian Gaussian is a command line driven computational chemistry application that applies both ab initio and semi empirical methods It is not included in ChemBio3D but may be purchased from PerkinElmer F Note Gaussian must be installed on the same system on which ChemBio3D is installed ChemBio3D provides an interface for Gaussian calculations This version supports all Gaussian calculations with these features a 13C and 1H NMR spectra predict
324. r selected atoms If all the atoms in a measurement are in a ring the set of moving atoms is generated as follows Only one selected atom that describes the measurement moves a f you set a bond length or distance between two atoms all atoms bonded to the non moving selected atom do not move Any atoms bonded to the moving atom move Ifthe Rectify check box in the Model Building tab go to File gt Model Settings and select the Model Building tab is selected rectification atoms that are positioned relative to an atom that moves may also be repositioned For example consider this structure Figure 5 3 Cyclopentylmethanol model If you set the bond angle C 1 C 2 C 3 to 108 degrees C 3 becomes the moving atom C 1 and C 2 remain sta tionary H 11 and H 12 move because they are bonded to the moving atom If the Automatically Rectify check box is selected H 10 may move because it is a rectification atom and is positioned relative to C 3 Setting constraints You can override the standard measurements that ChemBio3D uses to position atoms by setting constraints You can use constraints for a particular bond length bond angle dihedral angle or non bonded distance The constraint is then applied instead of the standard measurement when you use Clean Up or perform an aligning overlay or MM2 computation To set constraints enter a new value in the Optimal field of the Measurement table For dihedral angles and non bonde
325. r that is defined in the Elements table With the model explorer you can use different selection highlight colors for different fragments or groups The colors defined in the Elements table don t change when you do this In the model explorer you can change the default color of an object to a custom color To select a custom color right click the object and choose Color gt Select Color to revert to the default color right click the object in the model explorer and go to Color gt Apply Atom Color gt Inherit Atom Color a To select the custom color again right click the object and go to Color gt Apply Atom Color gt Apply Atom Color Groups You can select two or more atoms in your model and group them in a list in the model explorer After creating the group you can color all the atoms in the group hide them or change their display mode without having to select each atom You can also use groups to highlight part of a model such as the active site of a protein for visual effect Objects in group do not have to be connected to each other in your model and can consist of other groups atoms and bonds To create a group 1 Do one of the following n the model explorer hold down the CTRL key and select atoms you want in the group Chapter 4 Displaying Models 54 of 318 ChemBio3D 14 0 Perkin For the Better a n the model window hold the SHIFT key and select the atoms you want in the group 2 Inthe model explorer
326. r the RMS Gradient becomes less than the Minimum RMS Gradient value 10 Click Display Every Iteration 11 Click Start How the fragments are moved at each iteration of the overlay computation is displayed To stop the overlay computation before it reaches the preset minimum click Stop Calculation on the toolbar The overlay and recording operation stops Molecular surfaces A molecular surface displays information about an entire molecule as opposed to the atom and bond information that the structure display provides Surfaces show a molecule s physical and chemical properties They display aspects of the external surface interface or electron distribution of a molecule Before most molecular surface can be displayed the data necessary to describe the surface must be calculated using Extended H ckel or one of the methods available in Gaussian Solvent accessible surfaces do not require a calculation These surfaces are rendered from data in the parameters tables Surface types The surface types and the calculations necessary to display them are summarized in the table below f Note Spin Density map requires that CS MOPAC or Gaussian computations be performed with an open shell wave function Solvent Accessible Connolly Molecular Total Charge Density with Molecular Orbital map Chapter 4 Displaying Models 62 of 318 hemBio3D 14 I Che o3 0 PerkinElmer For the Better with Spin Density map No Yes with Partial Ch
327. r to add individual atoms to a selection SHIFT click each atom to add Deselecting atoms and bonds When you deselect an atom you deselect all adjacent bonds When you deselect a bond you deselect the atoms on either end if the atoms are not connected to another selected bond a SHIFT click an atom or bond to deselect it a Click an empty area of the Model window to deselect all atoms and bonds Changing elements To change an atom from one element to another Click the Build from Text tool Click the atom to change A text box appears Press ENTER 1 2 3 Type the symbol for the element you want case sensitive 4 5 Optional To apply the symbol again double click another atom Example To change benzene to aniline 1 Click the hydrogen atom to replace and type NH2 Chapter 3 Basic Model Building 19 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 2 Press ENTER amp Figure 3 3 aniline model Kukele and delocalized bonds Alternate double and single bonds in aromatics and other compounds can be displayed in either their Kekule or delo calized form Two typical examples CO and benzene appear below Figure 3 4 Kekule and delocalized bonds After building your model you can toggle between Kekule and delocalized bonds in any of three ways Inthe model window type CTRL K Goto View gt Model Display gt Delocalized Bonds and select an option Goto File gt Model Setti
328. r use experimental data to compensate for the simplification Note Gaussian 03 requires 32 bit version of Windows and Gaussian 09 requires either 32 bit version or 64 bit ver sion of Windows See Gaussian on page 104 for more information About CS MOPAC CS MOPAC performs semi empirical calculations on atoms and molecules to determine details of molecular struc tures and properties For example with CS MOPAC you can perform thermodynamic calculations geometry optim izations and force constant calculations CS MOPAC provides the functionalities of MOPAC through the ChemBio3D interface ChemBio3D supports MOPAC 2007 and MOPAC 2009 There are two CS MOPAC options available CS MOPAC Ultra and CS MOPAC Pro CS MOPAC Ultra includes all the capabilities of MOPAC and is available only as an optional plug in CS MOPAC Ultra provides support for advanced features such as MOZYME and PM5 methods Chapter 1 About ChemBio3D 1 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better With CS MOPAC Pro you can perform simple and advanced energy minimizations optimize to transition states and compute various properties Both CS MOPAC Pro and CS MOPAC Ultra supports MOPAC sparkles For more information see MOPAC on page 110 Note MOPAC sparkles are the extra eight elements added to MOPAC that represent pure ionic charges CS MOPAC is included in some versions of ChemBio3D or may be purchased as an optional plug in Contact Perk
329. r window with the structure displayed Inthe Suppliers list select a supplier from whom to order A list of products from the selected supplier appears Inthe product list select one or more products to order and click Add to Cart oOo a A O When you are ready click View Shopping Cart and complete your order 7 Note For information on how to order chemicals using ChemACxX click Help in the ChemACX main menu Chapter 3 Basic Model Building 33 of 318 ChemBio3D 14 0 PerkinElmer For the Better Displaying Models The display options in ChemBio3D not only let you add visual appeal to models but are also designed to help you examine structural properties Using basic tools you can scale rotate and move various objects in your model You can also add color to identify objects or show atomic distance and bond angle measurements Display modes Display modes define how bonds and atoms appear Models appear in the Ball amp Stick display mode by default To change the display mode go to View gt Model Display gt Display Mode and select a display mode option You can also change the display mode for model fragments See Display modes for fragments on page 57 The display modes are described below Setting the default display mode ChemBio3D applies the default display mode whenever you open a new model window To set the default display mode Go to File gt Model Settings The Model Settings dialog box appears Select th
330. rce field calculation methods 2 2 00 002 e cece cece cence eee ee een ee nce Aann nnna eeeeeeeeeeeees 88 Compute Properties s s esee cance Sad e eese ee Sedan Sdecss wqekensk sata ogden de Bees ese ee st 89 Calculating multiple properties 2 2 2 0 00000020 c coe ee eee ce eee eee cece ee eeeeeeeeeeeeeceeeseceeeeees 91 MM2 and MMFF94 202 22 ccc cece cece cece ee cece cece cece cece ceeceeeseeesseeeceeeeeseeesees 91 Gaussian 225 22 c052c5 aes ach oateulcs oahu Let oeete eet beye ate a dia ue st eid Siete eh alg 104 CONFLEX i idueier nate a a a a aa are aa La 109 MOPAGC eera a ea e a E a E EEE 110 CS GAMESS daea eea a r ade ge ic ae a E E E EEEE 133 Chapter 7 Parameter Tables _ 2 2 2 2222 coco cece cc ccc ccc cece cece ccc e cece eee ceceeeeececeeeeeeeeneeeees 138 TISTIOMOMNM Sie 2c 2245s gente eae ess eee a ces eis og eee EE EAEE EA 140 Building TYPOS sich cea et sore te Cate ee Sdn Sores neue iene ae eee 140 S bstr ct res table coson e a e e a eeeeccinledyiectadeedehetsmcdeiendouy 143 FREICICNCOS oar oE E a BI ec seei eae ca aie 144 Bond stretching parameters 0 00000 e cece eee e eee eeceeeeeeeeeeeeeeeeeeeeeeeeeeees 144 Angle bending parameters _ 2 0 20 222222 c cece cece cece cece Aa AA AA cece cee Aaaa aonana rnaen 145 Conjugated Pisystem bonds 2 22222 c eee cece cece cece cece cece Aa ea aaar aaran ronnan 146 PU PCOS seeps eae Ne 8 reper ease etn Me a ce a ea Ne ce ae ee tis ae 147 Ele
331. reaction with one or more steps Functions and Algorithms The secondary level consists of the core set of high level features that you can modify to meet your specific business needs Some examples are described below Template Based Normalization Enforce standard representations of functional group structures in chemical data Template Based Product Generation Automatic generation of products from a set of reactants and a generically defined reaction For example reactions like those between amines and carboxylates Chapter 10 ChemScript 184 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better Substructure Identification and Mapping Atom by atom comparison of a molecule with a substructure Positive matching provides an atom by atom map of the substructure atoms to those in the molecule Salt Stripping Remove salts from a reaction based on a pre defined list of salt fragments Structure Orientation Enforce standard orientation of structures based on the established orientation of a common scaffold 2D Structure Generation and Cleanup Use ChemBioDraw based algorithms to generate structure from scratch or after modifying chemical data using a pro gram Canonical Codes Generate unique identifying codes from a chemical structure File Format Conversion Read and write file data using all PerkinElmer supported file formats CDX CDXML MOL CHM SKC SMILES etc Chemical Name and Structure Conversion Use the Che
332. red bond and run a conformational analysis on it that will be used in both GAMESS min imizations For this tutorial we will choose the bond shown in red below Figure 17 31 The C 1 C 2 bond appears in red When analyzing the conformers of a bond you can set the angles of other bonds as desired For this tutorial we will set the C 1 C 2 C 3 C 4 dihedral bond angle to 90 degrees as follows 1 Inthe ChemDraw panel draw 2 phenylethanimine The molecule appears in the model window 2 Go to Structure gt Measurements gt Generate All Dihedral Angles The Measurement table appears 3 Inthe Measurement table select the C 1 C 2 C 3 C 4 bond 4 Inthe Actual column change the angle for the C 1 C 2 C 3 C 4 bond to 90 degrees and press ENTER Now that the dihedral bond is set we will run the conformation around the C 1 C 2 bond To run the conformation analysis 5 Inthe model window select the C 1 C 2 bond using the Move Objects tool Chapter 17 Tutorials 313 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 6 To run the conformation analysis go to Calculations gt Dihedral Driver gt Single Angle Plot The Dihedral Driver Chart opens displaying the conformational energy for the C 1 C 2 bond Dihedral Driver Chart x Conformational Energy 33 0 32 0 A 31 0 B 180 135 90 45 0 45 30 135 180 Energy kcal mol Figure 17 32 Dihedral chart for the C 1 C 2 bond in 2 phenylethan
333. rent atom combinations where force constants are available for describing the situation follow a X B C N O Y a B B C N O H a X AI S Y a X Al S H a X Si P Y a X Si P H a X Ga Ge As Se Y P Y where X and Y are any non hydrogen atom User imposed constraints Additional terms are included in the force field when constraints are applied to torsional angles and non bonded dis tances by the Optimal field in the measurement table These terms use a harmonic potential function where the force constant has been set to a large value 4 for torsional constraints and 106 for non bonded distances in order to enforce the constraint For torsional constraints the additional term and force constant is described by E 40 0 Torsions For non bonded distance constraints the additional term and force constant is E by 10 r r Distance Molecular dynamics simulation Molecular dynamics simulates molecular motion This simulation is useful because motion is inherent to all chemical processes vibrations like bond stretching and angle bending give rise to IR spectra chemical reactions hormone receptor binding and other complex processes are associated with many kinds of intramolecular and intermolecular motions Chapter 9 Computation Concepts 179 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better It is a time dependent method to simulate the movement of atoms Conformational transitions and loc
334. reo viewing To select whether the views are cross eyed or direct do one of the following a Select Reversed to rotate the right frame to the left If your left eye focuses on the right hand model and your right eye focuses on the left hand model the two stereo views can overlap a Select Parallel to rotate the right view further to the right Stereo enhancement ChemBio3D provides stereo graphics rendering for hardware that has stereo OpenGL capabilities There are a variety of stereo graphics cards stereo glasses and 3D monitors available To activate stereo enhancements 1 Go to File gt Preferences and select the OpenGL tab 2 Select Use Hardware Stereo when Available 3 Click OK Once the hardware is enabled stereo enhancement is available in any 3D window _ Note You must enable stereo in OpenGL in the display adapter properties control as well as in ChemBio3D pref erences and select the correct mode for the glasses monitor you are using You can use depth fading and perspective with hardware enhancement but should not activate other stereo modes Chapter 4 Displaying Models 71 of 318 ChemBio3D 14 0 PerkinE For the Better Controlling separation You can adjust the stereo effect by adjusting the eye separation 1 Go to File gt Model Explorer and select the Stereo amp Depth tab 2 Under General Stereo Settings adjust the Eye Separation slider 3 Click OK Setting view focus As models become larg
335. rest it is best to use a procedure that locates a transition state such as the CS MOPAC Optimize To Transition State command You can take these steps to ensure that a minimization has not resulted in a saddle point a Slightly alter the geometry and perform another minimization The new starting geometry might result in either a or f ina case where the original geometry led to c Apply the dihedral driver to search the conformational space of the model See Tutorial 5 The Dihedral Driver on page 299 a Run a molecular dynamics simulation which allows small potential energy barriers to be crossed After completing the molecular dynamics simulation you can then minimize and analyze individual geometries See MM2 ref erences on page 266 You can calculate these properties with the computational methods available through ChemBio3D using the PES Steric energy Heat of formation Dipole moment Charge density Chapter 9 Computation Concepts 166 of 318 ChemBio3D 14 0 Perkin For the Better a COSMO solvation in water a Electrostatic potential a Electron spin density a Hyperfine coupling constants a Atomic charges a Polarizability Others such as IR vibrational frequencies Choosing the best method Not all types of calculations are possible for all methods and no one method is best for all purposes For any given application each method poses advantages and disadvantages The choice of method depends on
336. rgy values for each point in the Output window O Tip To rotate the other dihedral angle other end of the bond right click in the Dihedral Driver Chart and choose Rotate other End Repeating the calculation We now need to turn the minimization off and repeat the calculation Right click the chart and select Recompute without Minimization This chart appears Chapter 17 Tutorials 317 of 318 ChemBio3D 14 0 PerkinElmer For the Better Dihedral Driver Chart Conformational Energy el 50 47 47kcal mol Energy kcal mol 180 135 90 45 0 45 90 135 180 C 2 Cf1 C 7 C 8 degrees Figure 17 36 Single angle plot of the diphenyl C C bond with minimization turned off Customizing the Dihedral Driver Chart By default the dihedral chart displays data in 5 degree increments To change this increment go to File gt Preferences and select the Dihedral Driver tab in the Preferences dialog box To customize the colors used in the chart select the color options in the Chart colors drop down lists Chapter 17 Tutorials 318 of 318
337. right click your selection and choose New Group from the context menu 3 Optional Rename the group by typing a new name Selecting a group To select a group click the group in the model explorer Expanding a group To expand or contract a group click its or icon Adding objects to groups You can add lower level objects to an existing group or combine groups to form new groups To add to a group 1 Inthe model explorer select the objects you want to add using either SHIFT click contiguous or CTRL click non contiguous 2 Right click your selection and choose New Group from the context menu 3 Rename the group if desired Note The order of selection is important The group or chain to which you are adding must be the last object you select Deleting groups You can delete the group without affecting its objects or the model You can also delete the group and all the objects within it a Select Delete Group to remove the grouping while leaving its contents intact a Select Delete Group and Contents to delete the group from the model Coloring groups Another way to view models is by assigning different colors to groups Changing a group color in the model explorer overrides the standard color settings in the Elements table and the Substructures table To change a group color 1 Select a group or groups 2 Right click the selected group s and choose Color gt Select Color on the context menu The Color Dialog
338. rigin atom and its distance defining atom Second if there are any rings in the model ring closing bonds are listed at the end of the file If there are ring closing bonds in the model a blank line is included after the last atom definition For each ring closure the serial numbers of the two atoms which comprise the ring closing bond are listed on one line The serial number of the first atom is 1 the second is 2 etc In the prior Internal coordinates output example of cyclohexanol the numbers 5 and 6 are on a line at the end of the file and therefore the ring closure is between the fifth atom and the sixth atom If a bond listed at the end of an Internal coordinates format file already exists because one of the atoms on the bond is used to position the other atom on the bond the bond is removed from the model This is useful if you want to describe multiple fragments in an internal coordinates file Chapter 14 File Formats 230 of 318 ChemBio3D 14 0 PerkinElmer For the Better Atom Type Text Numbers Bond Lengths Origin Atom 1 First Angles Second Atom 1 1 1 54146 Second Angles Third Atom 1 2 1 53525 1 111 7729 Fourth Atom 1 1 53967 2 109 7132 3 55 6959 0 Distance defining First Angle Second Angle Indicates Atoms defining Atoms defining Atoms Dihedral Figure 14 2 Components of an Internal coordinates File for C 1 through C 4 of Cyclohexanol In this illustration the origin atom is C
339. rivatives of potential energy g are then computed with respect to the new Cartesian coordinates New accelerations and velocities are computed at each step according to the following formulas m is the mass of the atom Chapter 9 Computation Concepts 180 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better ChemScript ChemScript is the cheminformatics Software Development Kit SDK It contains the programming algorithms that are common throughout PerkinElmer products As a software developer you can apply ChemScript to create your own scripts to use with ChemBioOffice applications All example script files in the ChemScript library are available in Python and C NET If you are familiar with either of these languages you will find these scripts easy to understand However if you are new to either Python or C NET we suggest that you refer to the Web sites and books listed at the end of this chapter Although ChemScript is available in Python and C NET we will use Python in this guide to explain ChemScript Python is a non proprietary and widely used programming language Why use ChemScript ChemScript adds considerable versatility to how you manage your chemical data Using ChemScript you can modify view and transfer your data from one place to another using your own custom rules Here are just a few common uses Salt splitting and stripping Identify and remove salt fragments from a drawn structure and register
340. rkinElmer For the Better Exchanging axes You can exchange the axes in a double angle dihedral chart Right click the chart and select Exchange Axis Recompute with minimization If your model contains distorted bonds typically by moving atoms you can minimize the energy and recompute the dihedral chart Click the chart and select Recompute with Minimization Peak Truncation In double dihedral charts you can truncate the high energy values in bad conformations to focus on more meaningful conformation To change the upper and lower bound of the legend click drag the top and bottom of the legend bar This changes the color map You can get the energy conformation at any point on the color map by clicking that point You can also focus on the local minima using peak truncation by dragging the upper bound and ignoring all con formations having higher energy than the upper bound value Setting graph colors Right click the chart to set the rotation interval used for the computation Once reset the dihedral computation is repeated with the new interval values You can also select display colors for the chart background coordinates and labels Setting graph resolution By default the conformational energy is calculated in 5 increments To change the resolution right click the chart select Set Resolution and choose a new value from the list Copying saving and printing the chart Right click the chart and choose from these options
341. rotation bars appear whenever you use them However you can always keep them hidden even when you are using them To hide display the rotation bars 1 Go to File gt Preferences and select the GUI tab 2 To show hide the rotation bars select deselect Show Mouse Rotation Zones 3 Click Apply and then click OK _ Note The rotation bars are active when you select the Rotate tool even if they are hidden Rotating around a bond To rotate the model around a bond 1 Select the bond using the Select tool 2 Using the Rotate tool drag the mouse along the Rotate About Bond Rotation bar on the left side of the Model win dow Chapter 4 Displaying Models 41 of 318 hemBio3D 14 I Seu PerkinElmer For the Better The rotation dial The rotation dial lets you specify an angle of rotation around a bond or a dihedral to create another conformation of your model To open the rotation dial click the arrow next to the Rotate tool Rotation Dial Figure 4 4 The Rotation dial A degree display box B Axis rotation C Local rotate around bond axis D dihedral rotation Rotating around a dihedral To rotate around a dihedral 1 Select either two or four adjacent atoms 2 Inthe rotation dial select one of the dihedral rotation options 3 Inthe rotation dial either enter a value in the degrees display box or click drag the dial to the desired angle Tip Use the keyboard shortcuts SHIFT B and SHIFT N to control which pa
342. rotation bars to see the final chair conformation _ Note The values of the energy terms shown here are approximate and can vary slightly based on the type of pro cessor used to calculate them This conformation is about 5 5 kcal mole more stable than the twisted boat conformation For molecules more complicated than cyclohexane where the global minimum is unknown other methods may be necessary for locating likely starting geometries for minimization One way of accessing this conformational space of a molecule with large energy barriers is to perform molecular dynamics simulations This in effect heats the molecule thereby increasing the kinetic energy enough to cross the energetically disfavored transition states Molecular dynamics Molecular Dynamics uses Newtonian mechanics to simulate motion of atoms adding or subtracting kinetic energy as the molecule s temperature changes Molecular Dynamics lets you access the conformational space available to a model by storing iterations of the molecu lar dynamics run and later examining each frame You can perform molecular dynamics simulation using either MM2 or MMFF94 Chapter 6 Computational Engines 100 of 318 ChemBio3D 14 0 PerkinElmer For the Better Molecular dynamics simulation using MMFF94 To perform a molecular dynamics simulation 1 Build the model or fragments to include in the computation _ Note The model display type you use affects the speed of the molecular dyn
343. rs 4 Type H Ala 120H and press ENTER 5 Rotate this structure to see the alpha helix that forms Changing model display To change the model display type 1 Click the arrow on the right side of the Model Display Mode tool on the Model Display toolbar 2 Select Wire Frame as the Model Type Tip You can also click the Display Mode icon Successive clicks cycle through the Display Mode options 3 Select the Rotate tool and rotate the model so you are viewing it down the center of the helix Chapter 17 Tutorials 295 of 318 PerkinElmer For the Better ChemBio3D 14 0 4 Use the Model Display Mode tool to choose Ribbons as the model type to see an alternative display commonly used for proteins Examining models Tutorial 4 Examining Conformations This tutorial uses steric energy values to compare the eclipsed and staggered conformations of ethane You first cre ate the staggered conformation and calculate the steric energy You then do the same for the eclipsed conformation Afterwards you compare the two steric energy values Figure 17 11 The steric energies of the eclipsed A and staggered B conformations of ethane are calculated in this tutorial To create the staggered conformation 1 Using the Single Bond tool IN draw a model of ethane in the model window 1 Select the Rotate tool on the Building toolbar 2 Click and drag to rotate the model 3 Stop dragging when you have an end on view of
344. rt of the model moves in the dihedral rotation A You can change the orientation of your model along a specific axis Although your model moves the origin of the model 0 0 0 does not change and is always located in the center of the model window To change the origin see Centering a selection on page 23 Rotating around a bond To rotate around a bond 1 Select either two adjacent atoms or a bond 2 Inthe rotation dial select the Local Axis option 3 Inthe rotation dial either enter a value in the degrees display box or click drag the dial to the desired angle Chapter 4 Displaying Models 42 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Atom and bond properties When you point to an atom or bond its properties appear in a pop up window Here is an example for an atom o 4 O Carboxylate Formal charge 1 Delocalized charge 0 50 This example is for a bond 7 C 1 C 2 to Length 1 509A The properties begin with the atom label such as C 1 for an atom or C 1 C 2 for a bond To choose other inform ation you want to appear go to File gt Preferences and select the Popup Info tab The options are described below Cartesian Coordinates Displays the three numerical values indicating the atom s position along the X Y and Z axes Atom Type Displays the atom type corresponding to the first column of a record in the Atom Types table Internal coordinates Lists the relative pos
345. s 116 of 318 hemBio3D 14 I enemBios 9 PerkinElmer For the Better f Note The GNORM property is not the same as the CS MOPAC keyword GNORM For more information see the MOPAC manual Dipole moment The dipole moment is the first derivative of the energy with respect to an applied electric field It measures the asym metry in the molecular charge distribution and is reported as a vector in three dimensions The dipole value will differ when you choose Mulliken Charges Wang Ford Charges or Electrostatic Potential as a dif ferent density matrix is used in each computation _ Note For more information see the MOPAC manual Charges This property determines the atomic charges using techniques discussed in the following sections In this example the charges are the electrostatic potential derived charges from Wang Ford because Wang Ford charges give useful information about chemical stability reactivity Mulliken charges This property provides a set of charges on an atom basis derived by reworking the density matrix from the SCF cal culation Unlike the Wang Ford charges uses Mulliken charges give a quick survey of charge distribution ina molecule _ Note For more information see the MOPAC online manual This contains the keywords sent to CS MOPAC MULLIK Sent to CS MOPAC to generate the Mulliken Population Ana lysis Sent to CS MOPAC to override checking of the Z matrix Sent to CS MOPAC to specify Molecular Mecha
346. s are present or quantitative determining how much of each are present To report perform an elemental analysis 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Elemental Analysis 3 Click OK Enthalpy Enthalpy is a property of a substance that can be used to calculate the heat produced or absorbed in a chemical reac tion Enthalpy is also a state function you can calculate the enthalpy change for a chemical reaction by finding the dif ference in enthalpy between the products and reactants Enthalpy is calculated using the formula H U PV Where a His enthalpy U is internal energy Pis pressure a Vis volume To calculate enthalpy 1 Go to Calculations gt Compute Properties Chapter 11 Chemical properties 195 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 2 Expand GAMESS Interface and select Enthalpy 3 Click OK Entropy The change of entropy dS is related to the amount of heat transfer dQ and temperature T by the formula _ dQ asa To calculate entropy using GAMESS 1 Go to Calculations gt Compute Properties 2 Expand GAMESS Interface and select Entropy 3 Click OK To calculate entropy using Gaussian 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select Entropy 3 Click OK This is the sum of the masses of the isotopes in a molecule For example the exact mass of water containing two hydrogen 1 1H and one oxygen
347. s is a good indication of the reactive site Predict IR spectrum A chart displaying the IR spectrum of the molecule selected can be generated To generate the IR spectrum 1 Go to Calculations gt Mopac interface gt Predict IR Spectrum The CS MOPAC Interface dialog box appears 2 On the Properties tab select Predict IR Spectrum from Job type list 3 Onthe Job amp Theory tab set the values of method wave function solvent and coordinate system 4 Click Run The Spectrum viewer displaying the chart appears Chapter 6 Computational Engines 130 of 318 ChemBio3D 14 0 PerkinElmer For the Better Spectrum Viewer x Mopac IR T TY CS MOPAC files Using output files Each computation performed using CS MOPAC creates a out file that contains all information about the com putation A summary arax file is also created where x increments from a to z after each run The out file is over written for each run but anew summary arax file is created after each computation araa arab and so on The OUT and AAX files are saved by default to the MOPAC Interface subfolder in your My Documents folder You may specify a different location from the General tab of the CS MOPAC Interface dialog box This information is found in the summary file for each run a Electronic Energy Eelectronic a Core Core Repulsion Energy Enuclear a Symmetry a lonization Potential a HOMO LUMO energies The out file contains t
348. s structures in SMILES notation either typed in or cut and pasted from other documents Chapter 17 Tutorials 293 of 318 ChemBio3D 14 0 Name Struct Another way to build this model is to use Name Struct To create the model using Name Struct 1 pP PerkinElmer For the Better Right click an empty space in the ChemDraw panel and select Structure gt Convert Name to Structure in the con text menu ChemDraw panel Inthe Insert Structure dialog box type 4 methy1 2 pentanol and click OK The structure appears in the So that model appears in the Model window ensure that LiveLink is selected at the top of the ChemDraw panel J Tip To temporarily activate the Select tool hold down the letter S on your keyboard while working with any build ing tool Stereochemistry You cannot specify stereochemistry when you build models with labels For example 1 2 dimethyl cyclopentane appears in the trans conformation by default However you can modify the default structure to show the cis isomer Figure 17 10 More complex models with the text box To illustrate first build the default structure 1 N DO oO fF OHN Go to File gt New _ Click Build from Text tool Click in the empty space in the model window Type 1 2 dimethyl cyclopentane Press ENTER The trans isomer appears Go to Edit gt Select All Go to Structure gt Clean Up Now invert it to display the cis isomer 1 2
349. s within a specified distance the bond proximate distance from one another can be automatically bonded ChemBio3D determines whether two atoms are proximate based on their Cartesian coordinates and the standard bond length measurement Pairs of atoms whose distance from each other is less than the standard bond length plus a certain percentage are considered proximate The lower the percentage value the closer the atoms have to be to the standard bond length to be considered proximate Standard bond lengths are stored in the Bond Stretching Parameters table To set the percentage value 1 Go to File gt Model Settings The Model Settings dialog box appears 2 Select the Model Building tab 3 Use the Bond Proximate Addition slider to adjust the percentage added to the standard bond length when ChemBio3D assesses the proximity of atom pairs You can adjust the value from 0 to 100 For example if the value is 50 then two atoms are considered proximate if the distance between them is no greater than 50 more than the standard length of a bond connecting them If the value is zero then two atoms are considered proximate only if the distance between them is no greater than the stand ard bond length of a bond connecting them To create bonds between proximate atoms 1 Select the atoms between which you want to create a bond 2 Go to Structure gt Bond Proximate If the two selected atoms are proximate a bond is created Setting meas
350. s you predict UV VIS IR and NUR spectra calculate energy and a number of other molecular properties Additional computational engines ChemBio3D supports several additional computational engines These tools are briefly mentioned below Their full descriptions are found in respective chapters of this guide For availability and purchase information contact PerkinElmer Informatics About Gaussian ChemBio3D supports Gaussian 03 and Gaussian 09 Gaussian is a property prediction program used by chemists chemical engineers biochemists physicists and other scientists Using the ab initio and semi empirical quantum mechanics Gaussian predicts the energies molecular structures vibrational frequencies and chemical properties of molecules and reactions in a variety of chemical environments You can apply Gaussian to both stable compounds and compounds that are difficult or impossible to observe experimentally such as short lived intermediates and trans ition structures Gaussian supports ab initio methods such as restricted and unrestricted Hartree Fock methods You can use ab initio and semi empirical methods for calculating electron density surface and molecular geometry optimization Gaussian supports ground state semi empirical methods such as CNDO 2 INDO MINDO3 and MDO energies and gradients _ Note The term semi empirical refers to methods that use the general process dictated by quantum mechanics but simplify it to gain speed and late
351. shee a ee ce eae ss ee Se ag ee A tan teste ee 218 ICIS CH OM aes cass tt a a ee Se eat Re ron gt Re 219 Chapter 13 2D to 3D Conversion _ 22 22 2 222 een ccc eee e cece cence cece ec ceeeteeeeeeees 221 Stereochemical relationships 2 22 0 222 e cece cece eee c cece cece ec cce cece eeeeeeceeeecceeeeeeeeeeeeeeees 221 kabels ttt te tode aye be hae S ete seca a eget ee atte ee teens te eeu alee ces ee asa heeoniie aie 223 Chapter 14 File Formats 2 2 22 00 0 20 2 ccc c cece cece eee c cece cence cece cece eee eee eceecceeeeeeeeeeeeeees 224 Editing file format atom types 0 00002 c occ c ccc eee cee ee cece cece bebe ee eeeeeeeeceeeeeeeeereeeeeees 224 Native formats 2 222222 ane resa Esia geet shes ey cS Sedudde de i testo ve lei delss Sb eee ge ide 2is se dens eek 224 File format examples 2 22 22222 e cece cece cece cece cc cece cece cece cece eee cece Ee aa dE EOE E E poi 224 EXport Tile Tomat lt 25 bocce ees yea ec canceeaae ts a Lae tee duel e a e 255 Chapter 15 References cso ieee ool eieteccn concen ececauencd eee duekebee bemavdee Gece adeaeeuln DADDA oaan aaan 265 MEP 55 eat ae a tse eee oe pee ease ee use g ee eee ee ite oat 265 MIMIZTETCNONCES lt 2 caste te eee ca ae has eco ee ea oN eee d 266 CS MORAG ae eh a ee Net A at ate ce ae es ites aac sda 268 Chapter 16 Online Resources 22 2 22 2 c cece cece nee e cece cece eee c cece cece eeeeceeeeeeeeeeeeeeees 282 SCIS c
352. sphate groups you can minimize see the ChemBio3D Drawing FAQ Conformation sampling Stochastic conformation sampling determines likely conformations of a molecule by starting with an initial structure its atomic coordinates and its defined bonds Each of the atoms initial X Y and Z coordinates are modified by the combination of random numbers to create a new random coordinate position The distorted conformation is then minimized using MMFF94 calculations and stored A new set of random numbers combined with the atomic coordinates and the steric energy of the new structure is then calculated To perform conformation sampling 1 Go to Calculations gt MMFF94 gt MMFF94 Stochastic Conformation Sampling A dialog box appears Chapter 6 Computational Engines 94 of 318 pP Perkin For the Better ChemBio3D 14 0 Specify the maximum random offset value in nm Specify the number of conformations to be displayed Specify the maximum number of steps of minimization a A WwW N Click Run The result appears in the output window _ Note The stochastic method of conformation sampling is not applicable to macromolecules 6 To view the conformations go to View gt Model Explorer and select from the fragment list Energy minimization using MMFF94 To perform an MMFF94 minimization 1 Go to Calculations gt MMFF94 gt Perform MMFF94 Minimization The Perform MMFF94 Minimization dialog box appears 2 Under Preferences tab
353. splay so that your results are similar to what you see in this guide To apply the default settings 1 Go to File gt Model Settings 2 Inthe Model Settings dialog box click Reset to Default 3 Click OK To view models as they appear in these tutorials 1 Go to View gt Toolbars gt Model Display 2 On the Model Display toolbar select the Display Mode drop down menu and choose Cylindrical Bonds Building models Tutorial 1 Building Models in 2D In this tutorial you build a model of phenol using the ChemDraw panel When you draw in the ChemDraw panel your two dimensional ChemBioDraw structure appears as a ChemBio3D model 1 Go to File gt New to open a new model window 2 Go to View gt ChemDraw Panel The ChemDraw panel opens Chapter 17 Tutorials 284 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 o Tip The ChemDraw panel is docked and hidden by default To keep the panel open when it is docked click the pin on the upper right Inthe top left corner of the panel select LiveLink 2 3 4 Click inthe ChemDraw panel The ChemDraw tools palette appears 5 On the ChemDraw tools palette select the Benzene tool 6 Click in the ChemDraw panel to draw a benzene ring The ChemDraw structure is converted to a 3D rep resentation fap ChemBio3D Ultra Untitled 1 x File Edit View Structure Calculations Surfaces Online Window Help DEHE oe Bei Ne Bee V 00 P Bi ERM OD SIPMANVN
354. splays a compiled list of all measurements of your model that you have generated After you generate the measurements you want you can select them from the table so that they appear in your model To open the measurement table go to View gt Measurement Table Chapter 4 Displaying Models 59 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better x Atoms Actual 7 Ap Opaionad t A a B 119 11x fad q i a Sad il Fx L z x e z l Figure 4 11 The Measurement table A Bond lengths B Bond angles 1 To generate measurements go to Structure gt Measurements gt Generate All Bond Lengths Bond Angles Dihedral Angles or Close Contacts The measurement table opens 2 To enable a measurement to appear in the model window select its corresponding Display check box 7 Note You can also modify measurements in the table see Setting measurements on page 77 Optimal measurements Optimal values are used instead of the corresponding standard measurements when a measurement is required in an operation such as Clean Up Structure Optimal measurements are used only when the Measurement table is visible When the Measurement table is not visible the standard measurements are taken from the parameter tables To specify optimal values for measurements edit the value in the Optimal column ChemBio3D also uses the optimal values with the Align command When you choose Structure gt Align
355. splays the opposite side 7 Select or deselect Show Surface Orbital to display or hide the surface 8 Click OK when finished Chapter 4 Displaying Models 70 of 318 hemBio3D 14 I ChemBio3 0 PerkinE For the Better Using stereo pairs Stereo Pairs is a display enhancement technique based on the optical principles of the stereoscope By displaying two images with a slight displacement a 3D effect is created 7 Note a stereoscope is a device for viewing photographs in three dimensions Stereo views can be either parallel or reverse direct or cross eyed Some people find it easier to look directly others can cross their eyes and focus on two images creating an enhanced three dimensional effect In either case the effect may be easier to achieve on a printed stereo view of your model than on the screen Keep the images relatively small and adjust the distance from your eyes Setting stereo pair parameters To set the stereo pairs parameters 1 Go to File gt Model Settings and click the Stereo amp Depth tab The stereo views control panel appears 2 Select Render Stereo Pairs to display two views of the model next to each other The right view is the same as the left view rotated about the Y axis 3 Specify the Eye Separation Stereo Offset with the slider This controls the amount of Y axis rotation 4 Specify the degree of separation using the Separation slider About 5 of the width is a typical separation for ste
356. ss of one molecule of a substance relative to the unified atomic mass unit u equal to 1 12 the mass of one atom of 12C Also called molecular mass To report the mass 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Mass 3 Click OK Melting Point Is the temperature at which a solid becomes a liquid at standard atmospheric pressure At the melting point the solid and liquid phase exist in equilibrium The formula to calculate melting point is AH T 28 AS Where T is the temperature at the melting point AS is the change in entropy of melting and AH is the change in enthalpy of melting To report the melting point 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Melting Point 3 Click OK This is the molecular formula of the compound To report the mass 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Molecular Formula 3 Click OK Mol Formula HTML This is the molecular formula written in HTML format You can copy and paste the output to an HTML file Chapter 11 Chemical properties 204 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Here is an example of the output for a model of aniline C lt sub gt 6 lt sub gt H lt sub gt 7 lt sub gt N To report the mol formula in HTML format 1 Go to Calculations gt Compute Properties 2 Expand ChemPropStd and select Mol Formula HTML 3 Click OK
357. ss style of color encod CMYK Contiguous Stores colors non sequentially For example CMYKCMYK The PackBits compression type provides no compression for this type of file ing F Note If objects in your document are black and white they are saved as black and white regardless of which Color options you set If you import drawings from other applications and want them to print Black and White you must set the Color option to Monochrome 4 Choose a compression option PackBits reduce file size by encoding repeating bytes of information as output For example for a line of color information such as CCCCCMMMMMYYYYYKKKKK the compression yields a smaller file by rep resenting the information as C5M5Y5K5 CCITT Group 3 or CCITT Group 4 fax transmissions of images GIF PNG and JPG Use the Graphics Interchange Format GIF Portable Network Graphics PNG file format or the JPEG format to publish a ChemBio3D model on the world wide web Each of these formats uses a compression algorithm to reduce the size of the file Applications that can import GIF PNG and JPG files include Netscape Com municator and Microsoft Internet Explorer The model window background color is used as the transparent color in the GIF format graphic f Note The size of the image in ChemBio3D when you save the file will be the same in your Web page If you tum on the Fit Model to Window building preference you can resize the window in ChemBio
358. st recent PM3 is a reparameterization of AM1 The approximations in PM3 are the same as AM1 This sequence of potential energy functions represents a series of improvements to support the initial assumption that complete neglect of diatomic orbitals would yield useful data when molecules proved too resource intensive for ab ini tio methods Adding parameters to MOPAC Parameters are in constant development for use with PM3 and AM1 potential functions If you find that the standard set of parameters that comes with CS MOPAC does not cover an element that you need for example Cu you can search the literature for the necessary parameter and add it at run time when performing a MOPAC job This flexibility greatly enhances the usefulness of MOPAC You can add parameters at run time using the keyword EXTERNAL name where name is the name of the file and its full path containing the additional parameters Using keywords Selecting parameters fora MOPAC approximation automatically inserts keywords in a window on the General tab of the MOPAC Interface You can edit these keywords or use additional keywords to perform other calculations or save information to the out file Caution Use the automatic keywords unless you are an advanced MOPAC user Changing the keywords may give unreliable results For acomplete list of keywords see the MOPAC online manual Chapter 15 References 269 of 318 ChemBio3D 14 0 PerkinElmer For the Better Aut
359. sting model 1 With the Build from Text tool click an atom in the model 2 Enter the name of the substructure see the first column in the Substructrure parameter table and press ENTER To create a new fragment from a substructure 1 Inthe Substructure parameter table right click the image of the substructure in the Model column and select Copy in the context menu 2 Right click the model window and select Paste in the context window Editing the substructure table To remove a substructure from the table 1 Click the row number for the substructure you want to remove The row is highlighted 2 Right click a highlighted cell in the row and select Delete row the row is removed To add a row to the table 1 Do ore of the following To add a row before an existing row right click the existing row and select Insert Row a To add a row at the bottom of the table right click any cell and select Append Row Inthe Name column in the new row add a name for the substructure Build the subtructure model in the model window Select the model Goto Edit gt Copy Inthe Substructure table right click the Model cell in the new row and select Paste Double click the Color cell and assign the substructure a color ON DOO FP WwW NY Close the Substructure window and save your changes when prompted Chapter 7 Parameter Tables 143 of 318 ChemBio3D 14 0 PerkinE For the Better References The References t
360. sults appear in the Output window and the Atom Property table To calculate Mulliken charges using Gaussian 1 Go to Calculations gt Compute Properties 2 Expand Gaussian Interface and select Mulliken Charges 3 Click OK An alternative method 1 Go to Calculations gt Gaussian Interface gt C ompute Properties 2 Inthe Properties tab select Mulliken Charges and click Run The results appear in the Output window and the Atom Property table Mulliken Populations Mulliken Population Analysis MPA is a partitioning scheme based on the use of density and overlap matrices of alloc ating the electrons of a molecular entity in some fractional manner among its various parts atoms bonds orbitals MPA is arbitrary and strongly dependent on the particular basis set employed However comparison of population ana lyses for a series of molecules is useful for a quantitative description of intra molecular interactions chemical react ivity and structural regularities According to MPA the Gross Orbital Population GOP is GOP YP v P is population matrix and is expressed for a closed shell as Chapter 11 Chemical properties 207 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 P DS S is the overlap matrix and D is density matrix If the coefficients of the basis functions in the molecular orbital are Ci for the uth basis function in the ith molecular orbital the density matrix terms are expressed as Dg
361. t to False Height Defines the height of the object window Left Defines the placement of the left edge of the object window Modified Cannot be changed Rock amplitude The amplitude in which the model will rock when the DemoMode is set to DemoRock ShowC ontextMenu Shows hides right click menus in the object window ShowRotationBar Shows hides the Rotation toolbar ShowToolbar Determines placement of the Toolbar left right top bottom or hides the toolbar Top Defines the top of the object window measured from the top of the slide ViewOnly Set to False by default Visible Shows hides the object window Width Defines the width of the object window Printing You can print your models to either an Adobe PostScript or non PostScript printer When you print your model you can specify several options such as the image scale and resolution To set print options 1 Go to File gt Print Setup The Print Setup dialog box opens 2 Inthe Printer drop down list select a printer 3 In the Form drop down list select the size of the paper 4 Select an orientation 5 Select from these options Scale To Full Page The model size is adjusted to the page size Scale to__ mm Angstrom Always print with White Background White will replace the background color that appears on the screen High resolution Printing Select for higher quality Deselect for faster printing Include a Footer A footer appears on the printed page
362. t to add a new job to the queue 3 optional To remove a job from the queue select the Link tab and click the button 4 Run the job queue To terminate the runs at any time click the stop button on the Calculations toolbar Partial optimizations To perform a partial optimization 1 Select a part of the model You may optimize either the selected or unselected portion 2 Go to Calculations gt Gaussian Interface gt Optimize to Transition state In the Gaussian Interface dialog box in the Coord System text window click Internal Coordinates 3 In the Move Which text window indicate whether the selected or un selected atoms are to be optimized 4 Click Run 7 Note If you use Gaussian 09 calculations are done on the Gaussian interface and you need to close the Gaus sian 09 interface to view the results in ChemBio3D Chapter 6 Computational Engines 105 of 318 ChemBio3D 14 0 Perkin For the Better Input template Input template is a template file in which certain fields are replaced with variables whose values are to be optimized The template file is used to construct an actual Gaussian input file containing the current values of the variables for each energy evaluation The energy is then computed at each step by running a Gaussian fixed point calculation The General tab of the Gaussian Interface dialog box contains the input template You can set output parameters with the check boxes and edit keywords in the run
363. table Include Serial Numbers Contain serial numbers Include Atom Type Text Numbers Contain atom type numbers Save All Frames Contain internal coordinates for each view of the model Connection Table ChemBio3D uses the atom symbols and bond orders of connection table files to guess the atom symbols and bond orders of the atom types There are two connection table file formats CT and CON The CON format is supported only for import When you save a file as a Connection Table an Options button appears in the Save As dialog box To specify the save options 1 Click Save As 2 Select the Conn Table format in the Save As dialog box 3 Select from these options 1 Blank Line add a blank line to the top of the file 2 Blank Lines add two blank lines to the top of the file 3 Blank Lines add three blank lines to the top of the file Gaussian Input Use the Gaussian Input GJC GJF file format to interface with models submitted for Gaussian calculations Either file format may be used to import a model Only the Molecule Specification section of the input file is saved For atoms not otherwise specified in ChemBio3D the charge by default is written as 0 and the spin multiplicity is written as 1 Chapter 14 File Formats 260 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better You can edit Gaussian Input files using a text editor with the addition of keywords and changing optimization flags for running the file usin
364. tages for using substructures a Substructures may be energy minimized a Substructures have more than one attachment atom bonding atom pre configured For example the substructure Ph for the phenyl group has a single attachment point The substructure COO for the carboxyl group has attachment points at the carboxyl carbon and the anionic oxygen Similar multi bonding sites are defined for all amino acid and other polymer units a Amino Acid substructures come in alpha and beta forms If the name of the amino acid is preceded by the symbol B then it implies that the acid is in beta form otherwise the acid is in alpha form The dihedral angles have been pre set for building alpha helix and beta sheet forms a You can use substructures alone or with single elements or atom types Chapter 3 Basic Model Building 25 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better a Using a substructure creates a record in the Groups table that you can use for easy selection of groups or coloring by group a Substructures are particularly useful for building polymers a You can define your own substructures and add them to the substructures table or create additional tables For more information see Defining substructures on page 24 a You must know where the attachment points are for each substructure to get meaningful structures using this method Pre defined substructures have attachment points as defined by standard chemistr
365. ted to molecules of 300 atoms or less Critical Pressure Reported in bars this is the least applied pressure required at the critical temperature to liquefy a gas To report the boiling point 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Critical Pressure 3 Click OK Chapter 11 Chemical properties 192 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Critical Temperature Reported in Kelvin this is the temperature above which a gas cannot be liquefied regardless of the pressure applied To report the boiling point 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Critical Temperature 3 Click OK Critical Volume Reported in cm mol this is the volume occupied by one mole of a substance at the critical temperature and pressure To report the boiling point 1 Go to Calculations gt Compute Properties 2 Expand ChemPropPro and select Critical Volume 3 Click OK Dipole Measured in Debye the dipole refers to the separation of charge between two covalently bonded atoms Dipoles can be characterized by their dipole moment a vector quantity with a magnitude equal to the product of the charge or mag netic strength of one of the poles and the distance separating the two poles Dipole moment is calculated using the for mula H aqr Where is the dipole moment q is the magnitude of the separated charge and ris a vector from the site of positive charge
366. tensions GAMESS Job F Note You must save the file in the GAMESS Job folder for it to appear in the menu 4 Select the jdf or jdt file type 5 Click Save Running a CS GAMESS job You can run an INP GAMESS job files in ChemBio3D To run the job file 1 Go to Calculations gt GAMESS gt Run a Job The Open dialog box appears 2 Type the full path of the CS GAMESS file or Browse to location 3 Click Open The appropriate dialog box appears 4 Change settings on the tabs if desired 5 Click Run Repeating a CS GAMESS job To repeat aCS GAMESS job 1 Go to the Calculations gt GAMESS gt Repeat name of computation The appropriate dialog box appears 2 Change parameters if desired and click Run Chapter 6 Computational Engines 137 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better Parameter Tables ChemBio3D uses parameter tables for building and analyzing your model These tables contain energy and topology data for elements bond types atom types and other parameters Since ChemBio3D uses these tables to build chem ically accurate models of actual molecules you typically will not want to edit the tables However the tables are avail able for expert uses to modify as desired If you choose to modify the tables remember that they must be kept in the C3D Items directory The parameter tables are 3 Membered Ring Angles Bond angles for bonds in 3 membered rings In force field analysis angle bending portio
367. ter 5 Building Advanced Models 87 of 318 ChemBio3D 14 0 PerkinElmer For the Better Computational Engines Computational chemistry applies chemistry mathematics and software to solve chemical problems It includes meth ods for calculating molecular properties or simulated experimental results Computational methods can be classified into these categories Force field calculation methods m Ab initio methods a Semi empirical methods The applications that implement these methods are called computational engines This section discusses several computational engines MM2 MMFF94 Gaussian CS MOPAC and CS GAMESS None of these methods is best for all purposes nor do any of them implement all three computational categories You must choose a method and a computational engine that suits your needs The choice of method depends on several factors including a The nature and size of the molecule The type of information sought a The availability of applicable experimentally determined parameters as required by some methods Computer resources To determine which engine to use to calculate a particular property see Chemical Properties Ab initio methods Ab initio methods are computational methods based on quantum chemistry In these methods molecular structures can be calculated using the Schr dinger equation values of the fundamental constants and atomic numbers of the atoms present The computational engines Gaussian an
368. ters to ensure atoms in trigonal planar geometry remain planar References Contains information about where parameter information is derived Substructures Contains predrawn substructures for fast model building Torsional Parameters Computes the portion of the force field for the torsional angles in your model VDW Interactions Adjusts specific van der Waals interactions such as hydrogen bonding When you build a model ChemBio3D 14 0 ensures that the bond lengths and angles in your model meet the criteria specified in the parameter tables Chapter 7 Parameter Tables 138 of 318 ChemBio3D 14 0 Perkin For the Better Applying parameters to a model To apply parameter tables to your model 1 Go to File gt Model Settings and select the Model Building tab 2 Select Apply Standard Measurements Deselect the Apply Standard Measurements option to build your model without the constraint of the parameter tables However since no parameters are being applied your model may not be accurate Estimated parameters In certain circumstances ChemBio3D may estimate parameters For example during an MM2 analysis assume a non MM2 atom type is encountered in your model Although the atom type is defined in the Atom Types table the necessary MM2 parameter will not be defined for that atom type For example torsional parameters may be missing This commonly occurs for inorganic complexes which MM2 does not cover adequately More parameters
369. that has been assigned to atoms and calculates the delocalized charge If an atom possess a delocalized charge that is different from the formal charge both charges are shown otherwise only the formal charge is displayed 1 untitled 1 b x ChemBioDraw Livelink qx Q Gy Ge Chem SMILEs oid O Nitro Formal charge 0 Delocalized charge 0 50 Origin Chapter 3 Basic Model Building 22 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Object position The position of every object in a model is defined by two sets of Cartesian coordinate axes the model axes and the view axes The model axes green determine the absolute position of all objects An object does not change its pos ition in relation to the model axes unless you move it The view axes purple define the relative position of all objects in the model The view axes origin is the center of all objects in the model As a result all objects in the model move relative to the view axes origin whenever an object is added deleted or moved in the model window Figure 3 5 A model showing both sets of coordinates The C 9 carbon is positioned at the origin of the model axes All objects in the model the two methane fragments are centered around the origin of the view axes Moving objects When you move an object you change its position in relation to the model axes For more information see Object position on page 23 1 Select the Move
370. the Molecular Simulations MolFile format are user definable For more information see Edit ing file format atom types on page 224 17 Line 48 contains the header for the Bond List section 18 Line 49 contains a listing of all the possible fields for the bond list section When the file is created by Chem3D Prothe following fields are used Bond Bond_type atom 1 atom 2 and cis trans and Qorder 19 Lines 50 68 each contain 4 fields describing information about each of the bonds in the structure the first field is the internal bond number 6 the second field is the bond type 1 the third and fourth fields are the atom serial num bers for the atoms involved in the bond atom 1 2 atom 2 16 the fifth field is the cis trans designator this is 0 if it does not apply the sixth through tenth fields are ignored and contain zeros if the file is created using Chem3D Chapter 14 File Formats 240 of 318 ChemBio3D 14 0 Perkin For the Better Pro the eleventh field contains the bond order S meaning single the twelfth and thirteenth fields are ignored and contain zeros if the file is created using Chem3D Pro 20 Lines 69 73 are each a section header for 3D conversion use This section only contains the header name only as shown when the file is created using Chem3D Pro 21 Line 74 is a header for the section User data area This section contains the header name only as shown when the file is created using Chem3D Pro 22 Li
371. the Rotate tool so that you can rotate your model to get a better view of what you are building Chapter 17 Tutorials 292 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 2 Double click two more hydrogens with the Move Objects tool W to change them to methyl groups y Tip The C you entered previously in the Text tool remains as the default until you change it You only have to double click with the Build from Text tool Saving the File To save the file 1 Go to File gt Save As 2 Type tut3a 3 Select a directory in which to save the file and click Save Save acopy of the model using the name tut3b These two copies of your model will be used in later tutorials Using Labels to Create Models You can also create models by typing atom labels element symbols and numbers in a text box For example to build 4 methy 2 pentanol shown below Figure 17 9 Creating a model with the text box 1 Go to File gt New or click the New tool on the Standard toolbar 2 Click the Build from Text tool 3 Click in the model window A text box appears 4 Inthe text box type either CH3CH CH3 CH2CH OH CH3 or 4 methyl 2 pentanol You type labels as if you were naming the structure pick the longest chain of carbons as the backbone and specify other groups as substituents Enclose substituents in parentheses after the atom to which they are attached 5 Press ENTER Tip The Text building tool also accept
372. the atom s changes to the new color To remove a custom atom color from the model display 1 Select the atoms whose colors you want to change 2 Right click the atoms you selected and go to Color gt Apply Object Color gt Inherit Object Color Coloring displays There are two ways for you to set the colors used to display your model You can set the colors either in the model set tings or in the model display menu a To apply colors using the model settings go to File gt Model Settings and select the Colors amp Fonts tab a To make atemporary change go to View gt Model Display gt Color By and select a menu option Chapter 4 Displaying Models 49 of 318 ChemBio3D 14 0 Perkin For the Better You can color by a Monochrome atoms and bonds are grayscale Chain Element atoms inherit the default color for the element they represent a Group atoms inherit the color assign to the group to which they belong if the group has been assigned a color Depth atom color is determined by its relative position along the Z axis f Note Monochrome and chain are available only for proteins displayed in the ribbon or cartoon display mode Coloring by element Color by element is the default mode for small molecules The default colors are stored in the Elements table To change the color of elements specified in the Elements table 1 Goto View gt Parameter Tables gt Elements The Elements table opens 2 Double click the Color fi
373. the bond stretching force constants standard bond lengths and twofold torsional barriers The basic process is 1 A Fock matrix is generated based on the favorability of electron sharing between pairs of atoms in a pi system 2 The pi molecular orbitals are computed from the Fock matrix 3 The pi molecular orbitals are used to compute a new Fock matrix then this new Fock matrix is used to compute better pi molecular orbitals 4 Step 2 and 3 are repeated until the computation of the Fock matrix and the pi molecular orbitals converge This method is called the self consistent field technique or a pi SCF calculation 5 A pi bond order is computed from the pi molecular orbitals 6 The pi bond order is used to modify the bond length BLres and force constant Ksres for each bond in the pi sys tem 7 The modified values of Ksres and BLres are used in the molecular mechanics portion of the MM2 computation to further refine the molecule Chapter 9 Computation Concepts 178 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better Stretch bend cross terms Stretch bend cross between bond stretching and angle bending For example when an angle is compressed the MM2 force field uses the stretch bend force constants to lengthen the bonds from the central atom in the angle to the other two atoms in the angle E X Kylr 1 Xo 0 Stretch Bend The force constant Kop differs for different atom combinations The seven diffe
374. the model window select at least one atom or group on the cavity boundary within the receptor Tip Consider selecting at least three atoms or groups in different locations along the boundary for a more accur ate cavity calculation Chapter 8 Docking 160 of 318 ChemBio3D 14 0 PerkinE ag For the Better 3 Click Centroid of the Selection AutoDock calculates the centroid of the cavity based on your selection s This is aconvenient tool to set the initial location of the grid box Alternatively you can click Set GridBox to Receptor Size to place a box around the whole structure 4 Optional To display the grid box in the model window select Display Grid Box The center of the grid box is posi tioned at the center of the cavity You can also choose a color for the grid from the drop down box 5 Under Centroid of the Grid Map enter X Y and Z coordinates to move the grid box as necessary 6 Under Number of Grid Points enter the number of grid points to use in the X Y and Z axes The grid box resizes as you edit the values F Note To change any of the X Y or Z values either enter a value in the text box or use the scroll arrows 7 Select the Spacing of Grids in Angstroms This grid box resizes after you enter a value 8 Optional To edit the GPF file manually click Edit under Advanced Options The GPF file opens in a text editor and you can make necessary changes j Caution It is not advisable to edit the GPF fi
375. the pure compound Canonical codes Generate canonical codes for a set of structures and use the codes to find duplicates in your data File format conversion Convert structure or reaction files from one format to another Generate properties Execute Struct Name or generate physical property features found in ChemBioDraw Common scaffold orientation Enforce standard orientations of structures based on the established orientation of a common substructure 2D Structure Diagram Generation SDG and Cleanup Generate new 2D structures from connection tables without coordinates and clean up existing 2D structure using the ChemBioDraw algorithms ChemScript lets you convert up to 10 000 data records per day For greater capacity you will need ChemScript Ultra For inform ation contact PerkinElmer Chapter 10 ChemScript 181 of 318 ChemBio3D 14 0 I i PerkinElmer For the Better How ChemScript works The most fundamental use for ChemScript is to read data from one source modify the data using a script and write the modified data to another location You can retrieve data from or write to almost any database file s or applic ation Figure 10 1 A ChemScript script can retrieve data from one source modify the data and write it to another location How the data is modified is determined entirely by the script The script can delete data calculate or add new data or edit existing data The data can be either text structures o
376. the selection by SHIFT clicking or SHIFT dragging across atoms You can also change building types and specify order of attachment The Build from Text tool lets you enter text either directly or using the Table editor 1Ionic compounds may consist of multiple fragments one for each ion Chapter 3 Basic Model Building 16 of 318 ChemBio3D 14 0 Perkin For the Better _ Note For all discussions below all the Model Building tab options in the Model Settings dialog box are assumed to be tumed on Using symbols and formulae Using the Build from Text tool you can use chemical symbols and formulae to build models To use an element symbol 1 Select the Build from Text tool 2 Click in the model window and type C 3 Press ENTER A model of methane appears The atom type is assigned as C Alkane and the appropriate number of hydrogens are added To use the same text to add another methyl group 1 Point to the atom you want to replace in this example a hydrogen and click The text box appears with the pre vious label 2 Press ENTER To add a different element 1 Click a hydrogen atom A text box appears over the atom 2 Type N and press ENTER A nitrogen is added to form ethylamine To build ethylamine in one step 1 Click in the model window A text box appears 2 Either type CH3CH2NH2 orethylamine 3 Press ENTER The Table editor To build models using the Build from Text tool you can use the Table editor t
377. tide saccharide Gas phase or implicit solvent environment Ground transition and excited states Ab initio methods available in ChemBio3D 14 0 with Gaussian apply to Systems containing up to 150 atoms Organic organometallics and molecular fragments catalytic components of an enzyme Gas or implicit solvent environment Study ground transition and excited states certain methods Chapter 9 Computation Concepts 168 of 318 ChemBio3D 14 0 Molecular Mechanics Gaussian Uses classical physics Relies on force field with embedded empirical para meters Semiempirical MOPAC Gaussian Uses quantum physics Uses experimentally derived empirical para meters Uses approximation extensively ab initio Gaussian CS GAMESS Uses quantum physics Mathematically rigorous no empirical parameters Least intensive com putationally fast and useful with limited com puter resources Can be used for molecules as large as enzymes Less demanding com putationally than ab initio methods Capable of calculating transition states and excited states Useful for a broad range of systems Does not depend on experimental data Capable of calculating transition states and excited states Figure 9 2 Comparison of Methods Chapter 9 Computation Concepts Particular force field applic able only for a limited class of molecules Does not calculate elec tronic properties Requires
378. tine You are increasing the force constant for the torsional term in the steric energy calculation so that you can optimize to the transition state 1 Select the Rotate tool 2 Reorient the model by dragging the X and Y axis rotation bars until you have an end on view Figure 6 2 Ethane model end on view To force a minimization to converge on the transition conformation set the barrier to rotation 1 Inthe Measurement table type O inthe Optimal column for the selected dihedral angle and press ENTER 2 Go to Calculations gt MM2 gt Minimize Energy The Minimize Energy dialog box appears Chapter 6 Computational Engines 97 of 318 ChemBio3D 14 0 PerkinElmer For the Better 3 Click Run Nw C Figure 6 3 Minimized ethane end on view When the minimization is complete the model conforms to the eclipsed structure and the reported energy values appear in the Output window The energy for this eclipsed conformation is higher relative to the staggered form The majority of the energy contribution is from the torsional energy and the 1 4 van der Waals interactions F Note The values of the energy terms shown here are approximate and can vary slightly based on the type of pro cessor used to calculate them Output x NM Minimization ji a Note All parameters used are finalised Quality 4 Iteration 159 Minimisation terminated normally becau Stretch 0 0443 Bend Stretch Bend o Torsion Non 1 4 VDU 1 4 Vow
379. tion If a surface is unavailable the command is grayed out in the submenu To generate surfaces from CS MOPAC or Gaussian you must choose Molecular Surfaces as one of the properties calculated by these programs Chapter 4 Displaying Models 63 of 318 Bio3D 14 I chempiga 9 PerkinElmer For the Better Surface display types ChemBio3D offers four different types of surface displays each with its own properties These types are shown in the following table The surface is displayed as an opaque form Solid is a good choice when you are interested in the details of the surface itself and not particularly interested in the underlying atoms and bonds Wire Mesh The surface is displayed as a connected net of lines Wire Mesh is a good choice when you want to focus on surface features but still want some idea of the atoms and bonds in the structure The surface is displayed as a series of unconnected dots Dots are a good choice if you are primarily interested in the underlying structure and just want to get an idea of the surface shape The surface is displayed in solid form but is partially transparent so you can also see the atoms and bonds within it Translucent is a good compromise between surface display styles Surface resolution The Surface Resolution is a measure of how smooth the surface appears The higher the resolution the more points are used to calculate the surface and the smoother the surface appears However
380. tion more than once or ona different computer You must have Gaussian installed to create an input file 1 Open or create a model 2 Go to Calculation gt Gaussian Interface gt Create Input File 3 Click Create Running an input file If you have a previously created GJF Gaussian input file you can run the file in ChemBio3D To run a Gaussian input file 1 Go to Calculations gt Gaussian Interface gt Run Input File The Run Gaussian Input file dialog box appears 2 Type the full path of the Gaussian file or Browse its location 3 Select the appropriate options a Show Output in Notepad Save the output to a file b Send Back Output Display the results in the Output window 4 Click Run Chapter 6 Computational Engines 108 of 318 ChemBio3D 14 0 Perkin For the Better The input file runs At a certain point a new tab opens and the model appears in the Model Window Running a Gaussian job ChemBio3D lets you select a previously created Gaussian Job Description File JDF The JDF file can be thought of as aset of Settings that apply to a particular dialog box You can create a JDF file from the dialog box of any of the Gaussian calculations Minimize Energy Optimize to Transition State by clicking Save As after all Settings for the calculation have been set For more information about JDF files see Job description file formats on page 108 To run a Gaussian job 1 From the Gaussian submenu choose Run Gaussian Job
381. tions the R and Eps values from the van der Waals Interactions table are used instead of values in the MM2 Atom Types table See van der Waals Interactions for more information Reduct Reduct is a constant used to position the center of the electron cloud on a hydrogen atom toward the nucleus of the carbon atom to which it is bonded by approximately 10 of the distance between the two atoms Any atom in a van der Waals potential function must possess a spherical electron cloud centered about its nucleus For most larger atoms this is a reasonable assumption but for smaller atoms such as hydrogen it is not Molecular mechanics calculations based on spherical electron clouds centered about hydrogen nuclei do not give accurate res ults However it is areasonable compromise to assume that the electron cloud about hydrogen is still spherical but that it is no longer centered on the hydrogen nucleus The Reduct constant is multiplied by the normal bond length to give a new bond length which represents the center of the repositioned electron cloud The value of the Reduct field for all non hydrogen atoms is zero Atomic weight The fifth field Atomic Weight is the atomic weight of atoms represented by this atom type number f Note The atomic weight is for the isotopically pure element For example the atomic weight for atom type number 1 is 12 000 the atomic weight of 12C Lone pairs The Lone Pairs field contains the number of lone pa
382. tively small molecules f Note To precisely reproduce the energies obtained with Allinger s force field set the van der Waals cutoff con stants to large values in the MM2 Constants table Electrostatic energy The electrostatic energy is a function of the charge on the non bonded atoms q their interatomic distance fip and a molecular dielectric expression D that accounts for the attenuation of electrostatic interaction by the environment solvent or the molecule itself In ChemBio3D the electrostatic energy is modeled using atomic charges for charged molecules and bond dipoles for neutral molecules ChemBio3D accounts for these interactions a charge charge dipole dipole dipole charge Each type of interaction uses a different form of the electrostatic equation qiq E Electrostatic 2 2o i j Dr Chapter 9 Computation Concepts 176 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better charge charge contribution p qidi E 332 05382 X where the value 332 05382 converts the result to units of kcal mole dipole dipole contribution HiH E 14 388 gt x cosx 3cos cosa 5 st ry where the value 14 388 converts the result from ergs mole to kcal mole x is the angle between the two dipoles Hj and Hj 0 and are the angles the dipoles form with the vector i connecting the two at their midpoints and Di is the effective dielectric constant dipole charge contribution
383. tom The greatest positive charge is on the adjacent car bon atom with the adjacent hydrogen atom a close second The rest of the molecule has relatively pale atoms their partial charges are much closer to zero Before starting the tutorials we recommend that you choose the default settings and an appropriate display so that your results are similar to what you see in this guide To use the default settings 1 Go to File gt Model Settings 2 Inthe Model Settings dialog box click Reset to Default 3 Click OK To view models as shown in these tutorials 1 Go to View gt Toolbars gt Model Display 2 On the Model Display toolbar select the Display Mode drop down list and choose Cylindrical Bonds Using calculation engines Tutorial 11 Rotamer Analysis In this tutorial we use GAMESS to identify the preferred lowest energy conformer around a specified bond in a simple molecule To identify the conformer we run conformational analysis on the molecule and then perform a GAMESS minimization calculation on each of two of its conformers one above a local energy minimum and another above the global energy minimum We then compare the results of the calculations We will use 2 phenylethanimine as the molecule For the purpose of this tutorial we will number the atoms as shown below Chapter 17 Tutorials 312 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 Figure 17 30 2 phenylethanimine We need to select the desi
384. tor Chapter 5 Building Advanced Models 86 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better 233 s92 LL 73 978 2 109 1 180 99 1 119 3 180 989 2 119 5 3 180 988 2 119 3 0 mmaenmoana PRPNHOWNHE COCO OFRF Building models using ISIS Draw To build a model using ISIS Draw 1 Draw a structure in ISIS Draw 2 Copy the structure to the clipboard 3 InChemBio3D go to Edit gt Paste F Note You can paste a model from ISIS Draw into the Model Window but not into the ChemDraw panel After your model appears in the Model Window you can synchronize the window so that the drawing appears in the ChemDraw panel Lone electron pairs Some molecules such as amines and carboxylic acids have lone electron pairs that you can add or remove when modifying your model After you add an electron pair you can show or hide the electrons without chemically changing your model Adding lone pairs To add a lone electron pair to your model go to Structure gt Lone Pairs gt Add Removing lone pairs To remove an electron pair go to Structure gt Lone Pair and select Remove Showing hiding lone pairs You can specify whether electron pairs are hidden or displayed _ Note Hidden electron pairs are still part of the model To show or hide lone pairs do one of the following Goto Structure gt Lone Pair and select either Add Show or Hide Goto View gt Model Display gt Show Lone Pairs and select either Hide or Show Chap
385. trength of a bond between two atoms The larger the value of KS value the more difficult it is to compress or to stretch that bond Length The third field Length contains the bond length for a particular bond type The larger the number in the Length field the longer is that type of bond Bond Dpl The Bond Dpl field contains the bond dipole for a particular bond type The numbers in this cell indicate the polarity of the bond A zero value indicates that there is no difference in the electronegativity of the atoms in a par ticular bond A positive bond dipole indicates that the building type represented by the first atom type number in the Bond Type field is less electronegative than the building type represented by the second atom type number Finally a negative bond dipole means that the building type represented by the first building type number in the Bond Type field is more electronegative than the building type represented by the second atom type number For example the 1 1 bond type has a bond dipole of zero since both alkane carbons in the bond are of the same elec tronegativity The 1 6 bond type has a bond dipole of 0 440 since an ether or alcohol oxygen is more electronegative than an alkane carbon Finally the 1 19 bond type has a bond dipole of 0 600 since a silane silicon is less electronegative than an alkane car bon Chapter 7 Parameter Tables 144 of 318 hemBio3D 14 I ChemBio3 0 PerkinElmer For the Better _ Note
386. tro files ChemBio3D supports the Schrodinger Maestro file format MAE for importing and exporting molecular models Molecular Design Limited MolFile The MDL Molfile format saves files by MDL applications such as ISIS Draw ISIS Base MAACS and REACCS The file format is defined in the article Description of Several Chemical Structure File Formats Used by Computer Pro grams Developed at Molecular Design Limited in the Journal of Chemical Information and Computer Science Volume 32 Number 3 1992 pages 244 255 Use this format to interface with MDL s ISIS applications and other chemistry related applications Both import and export are supported MSI ChemNote Use the MSI ChemNote MSM file format to interface with Molecular Simulations applications such as ChemNote The file format is defined in the ChemNote documentation Both import and export are supported MOPAC Files MOPAC data may be stored in MOP DAT MPC or 2MT file formats ChemBio3D can import any of these file formats and can export MOP files You can edit MOPAC files using a text editor adding keywords and changing optimization flags and run the file using the Run MOPAC Input file command within ChemBio3D Select Save All Frames to create a MOPAC Data file in which the internal coordinates for each view of the model are included The initial frame of the model contains the first 3 lines of the usual MOPAC output file see the example file below Each subsequent frame
387. troduces three cutoff techniques that prevent van der Waals calculations from scaling in time as the number of atoms increases a Shift function Switching function Truncation function To perform van der Waals calculation 1 Go to Calculations gt MMFF94 gt Perform MMFF94 minimization The Perform MMFF94 Minimization dialog box appears 2 Click the van der Waals Calculations tab 3 Torun the calculation using a cutoff technique un check Exact calculation 4 Select a cutoff technique and set the value of its corresponding parameter 5 Click Run The output window displays the calculation result Energy minimization When you build your model the location for each atom may not accurately represent the atom s location in the actual molecule Your model may depict high energy strain at various bonds or conformational strain between atoms As a result your model may not accurately represent the molecule To correct your model perform an MM2 or MMFF94 energy minimization calculation When you do ChemBio3D examines your model and identifies its various atom types It then calculates a new position of each atom so that the cumulative potential energy for your model is minimized Having calculated each new position ChemBio3D moves each atom in your model so that the total energy is at a minimum You cannot minimize energy in models containing phosphate groups drawn with double bonds For information on how to create a model with pho
388. ts the block named STRT This block contains the molecule name The molecule name is the file name when the file was created using Chem3D Pro 2 Line 2 starts the block named DTCR The information in this line includes the name of the application that created the file and the date and time when the file was generated 3 Line 3 starts the block named CT which contains the connection table of the compound s Also on this line is a 10 character description of the connection table This will be the same as the file name when the file is generated using Chem3D Pro Finally the number of records contained within the CT block is indicated 39 in the above example 4 Line 4 of the CT Block contains four fields The first field is the number of atoms the second field is the number of bonds the third field is the FORTRAN format for the number of atoms and the fourth field is the FORTRAN format for the number of bonds 5 Lines 5 23 of the CT Block each contain 4 fields describing an atom The first field is the element symbol first let ter uppercase second lowercase The second field is the total number of hydrogens attached to the atom the third field is the stereo information about the atom and the fourth field is the formal charge of the atom 7 Note If the file is created using Chem3D Pro the number of hydrogens the stereo information and the formal charge fields are not used and will always contain zeros Chapter 14 File Formats 249 o
389. ts to Output Box view the value of each measurement in the Output window Select Move Only Selected Atoms restrict movement of a selected part of a model during the minimization Calculation results are not affected _ Note To interrupt a minimization in progress click Stop in the Computing dialog box _ Note Before changing MM2 constants first make a backup copy of the parameter tables Chapter 6 Computational Engines 95 of 318 ChemBio3D 14 0 Perkin For the Better Note ChemBio3D guesses parameters if you try to minimize a structure containing atom types that MM2 does not support Data for each iteration appears in the Output window when the calculations begin However if you have not selected the Copy Measurements to Output option only the last iteration is displayed After the RMS gradient is reduced to less than the requested value the minimization ends and the final steric energy components and total appear in the Output window Intermediate status messages may appear in the Output window A message appears if the minimization terminates abnormally usually caused by a poor starting conformation You can perform any action in ChemBio3D that does not move add or delete any part of the model For example you can move windows during minimization change settings or scale your model Energy minimization examples Ethane Ethane provides a simple example of minimization because it has only one minimum energy staggere
390. tter ChemBio3D 14 0 Zoom and translate Move all Move the selected center rotation cen selection If you have a wheel mouse you can also use the scroll wheel to zoom Dragging with the middle button or scroll wheel translates the view Selection Standard selection Hold down the S key to choose the selection tool With the S key pressed you can perform the actions shown in the table below Select anatom Select multiple atoms or bonds Select multiple atom or bonds in Multiple box or bond as you click them within a region select atom bonds Note Clicking a bond selects the bond and the two atoms connected to it Double clicking an atom or bond selects the fragment that atom or bond belongs to Double clicking a selected fragment selects the next higher fragment that is each double click moves you up one in the hierarchy until you have selected the entire model Radial selection Radial selection is selection of an object or group of objects based on the distance or radius from a selected object or group of objects This feature is useful for highlighting the binding site of a protein Radial selection is accessed through the Select submenu of the context menu in the model explorer or 3D display Chapter 12 Keyboard modifiers 219 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 In all cases specify multiple selections by holding the SHIFT key down while making the selections Select Atoms wit
391. uctures connect Several predefined substructures are listed in the substructures table substructures xml file You can define your own substructures and add them to the table See Defining substructures on page 24 To apply a subtructure to a model you can either add it to an existing fragment by replacing one of the fragment s atoms with the substructure or you can paste the subtructure into the model window as a new fragment To apply a subtructure to a model 1 Go to View gt Parameter Tables gt Substructures 2 Inthe substructures table right click the Name of a substructure and select Copy 3 In your model do one of the following a To add the substructure to an existing fragment right click an atom in the fragment and select Paste a To add the substructure as a new fragment right click an empty area of the model window and select Paste Defining substructures To select a substructure 1 Build a model Part or all of the model must include the atoms you want to define as the substructure You can use ChemBio3D tools or build it in the ChemDraw panel 2 Inthe model select the part or all of the structure you want to define as the substructure 3 Goto Edit gt Copy To save the substructure definition 1 Goto View gt Parameter Tables gt Substructures to open the substructures window 2 Right click in the Substructures table and choose Append Row A new row is added to the table 3 Select the cell in the Model co
392. unction Molecular Electrostatic Potential The Molecular Electrostatic Potential MEP represents the attraction or repulsion between a molecule and a proton Attraction is represented by negative values and repulsion is indicated by positive values Experimental MEP values can be obtained by X ray diffraction or electron diffraction techniques and provide insight into which regions of a molecule are more susceptible to electrophilic or nucleophilic attack You can visualize the relative MEP values by color when MEP is mapped onto another surface total charge density The most positive MEP value is red the most negative blue and neutral is white For more information on MEP see MEP on page 265 Partial surfaces Scientists who study protein ligand interactions are often interested in generating a molecular surface of a protein that does not include a ligand ChemBio3D Ultra can generate partial Solvent Accessible and Connolly surfaces either by excluding ligands or by excluding selected parts of the model or both To generate a partial surface 1 Go to Surfaces gt Advanced Molecular Surfaces Chapter 4 Displaying Models 69 of 318 pP PerkinElmer For the Better ChemBio3D 14 0 2 Select the surface type and what you want to include and exclude in the Advanced Molecular Surfaces dialog box Solvent atoms are excluded by default but may be included with the check box Hidden atoms usually hydrogens may also be included
393. ure to save the PDB file again Backbone The backbone object is a display feature that lets you show the carbon nitrogen backbone structure of a protein It appears in the model explorer as a separate object with no children The atoms and bonds that make up the backbone belong to other chains and groups but are also virtual children of the Backbone object This lets you select display properties for the backbone that override the display properties of the chains and groups above them in the hierarchy Hiding objects Each object listed in the model explorer has a color coded icon next to it The color signifies the visibility status of the object Green The atom is visible Red The fragment or atom is hidden but still present Blue The fragment or atom visibility is inherited from its parent group or fragment To change hide or display a fragment or atom 1 Inthe model explorer select the fragment or atom 2 Select Visibility from the context menu and choose an option a Inherit Settings a Show Fragment or Atom a Hide Fragment or Atom Selecting objects You can select atoms and bonds using the model explorer in several ways a Select a single atom or bond a Select multiple atoms one atom at atime a Define a group of atoms and select the group a Select atoms or groups based on distance or radius To select an atom in the model explorer click it To select more than one atom hold down either the SHIFT or
394. urements When you build a model ChemBio3D uses a set of standard length and angle measurements to determine where to locate atoms in relation to each other You can override the standard measurements as desired To view the standard measurements used in your model go to Structure gt Measurements gt Generate All Bond Lengths or Bond Angles Standard measurements appear in the optimal or equilibrium column in the Meas urement table To edit a measurement values in your model replace the desired value in the Actual column of the measurement table and press ENTER You are not limited to viewing only the standard measurements You can also display distances between dihedral angles and non bonded atoms For how to modify measurements see Setting constraints on page 79 Setting bond lengths You can set the lengths between two atoms that share a covalent ionic or hydrogen bond To set the length of a bond between two atoms 1 Select the two atoms Chapter 5 Building Advanced Models 77 of 318 hemBio3D 14 I ChemBio3 0 Perkin For the Better 2 Go to Structure gt Measurements gt Display Distance Measurement The Measurement table appears displaying the distance between the atoms 3 Click and edit the value in the Actual column 4 Press ENTER Setting bond angles To set a bond angle 1 Select the three contiguous atoms that define the angle 2 Go to Structure gt Measurements gt Display Bond Angle Measurement The Measur
395. v Figure 4 6 Selecting atom for alignment 3 Go to View gt View Position gt Align View Z Axis With Selection Aligning to a plane You can align your model to any Cartesian coordinate plane that you define To align a model to a plane you first select at least three atoms to define the plane If you select more than three atoms a plane is computed that min imizes the average distance between the selected atoms and the plane commonly known as the best fit plane To align the model to a plane 1 Select three or more atoms 2 Go to Structure gt Model Position gt Align Model choose a plane With Selection The model rotates so that the computed plane is parallel to the plane you choose X Y Y Z or X Z To move three atoms to a plane and two of the atoms onto an axis 1 Select the two atoms 2 Go to View gt View Position gt Align View choose an axis With Selection 3 SHIFT click the third atom Chapter 4 Displaying Models 47 of 318 ChemBio3D 14 0 I i PerkinElmer For the Better 4 Go to View gt View Position gt Align View choose a plane With Selection For example to move a cyclohexane chair so that three alternating atoms are on the X Y Plane 1 Select two non adjacent carbon atoms in the ring 2 Go to View gt View Position gt Align View X Axis With Selection The model moves to the position shown in Figure B 3 Select the third non adjacent carbon atom in the ring 4 Go to View gt View Position gt Ali
396. viewed as a strain energy imposed by a model moving from some ideal zero strain conformation Stretching energy bond stretching between directly bonded atoms Bending energy angle bending between two atoms that are adjacent to a third atom Torsion energy torsional angle rotation between atoms that form a dihedral angle Non bonded interaction energy The non bonded interaction include these two forces a Repulsion for atoms that are too close and attraction at long range from dispersion forces van der Waals inter action Chapter 9 Computation Concepts 171 of 318 h Bio3D 14 I ChemBio3 0 PerkinElmer For the Better Interactions from charges dipoles quadrupoles electrostatic interactions This illustration shows the major interactions A Figure 9 3 Potential Energy Interactions A non bonded interactions B angle bending C bond stretching D tor sion Different force fields have been developed Some include additional energy terms that describe other deformations such as the coupling between bending and stretching in adjacent bonds to improve the accuracy of the mechanical model MM2 ChemBio3D uses a modified version of Allinger s MM2 force field For additional MM2 references see MM2 ref erences on page 266 The principal additions to Allinger s MM2 force field are Acharge dipole interaction term a A quartic stretching term Cutoffs for electrostatic and van der Waals terms with 5th order p
397. wo dimensional structures ChemBio3D uses standard bond lengths and angles as specified in the current set of parameters If ChemBio3D tries to translate strained ring systems the ring closures will not be of the correct length or angle Chapter 13 2D to 3D Conversion 222 of 318 ChemBio3D 14 0 PerkinElmer For the Better Labels ChemBio3D uses the atom labels in a two dimensional structure to determine the atom types of the atoms Unlabeled atoms are assumed to be carbon Labels are converted into atoms and bonds using the same method as that used to convert the text in a text box into atoms and bonds Therefore labels can contain several atoms or even substructures Chapter 13 2D to 3D Conversion 223 of 318 ChemBio3D 14 0 PerkinElmer For the Better File Formats Editing file format atom types Some file formats contain information that describes the atom types Typically these atom types are ordered by some set of numbers similar to the atom type numbers used in the Atom Types table If the file format needs to support addi tional types of atoms you can supply those types by editing the file format atom types ChemBio3D uses XML tables to store file formats You can edit these tables in any text editor or in ChemBio3D Go to View gt Parameter Tables and select the table you want to edit Tip The XML files are in the path Chem3D C3D Items Name Each atom type is described by aname This name is a number fou
398. xml contains the atom types used in building models Normally you use only the first column of the table while building models To use a building type in a model type its name in the Replacement text box or paste it after copying the name cell to the Clipboard and press ENTER when an atom is selected or when you double click an atom If no atom is selected a fragment is added The fields that comprise a building type record are described below Name The records are ordered alphabetically by atom type name Building type names must be unique Symbol This field contains the element symbol associated with the building type The symbol links the Chem3D Building Atom Types table and the Elements table The element symbol is used in atom labels and when you save files in file formats that do not support building types such as MDL MolFile van der Waals Radius The van der Waals van der Waals radius specifies the size of atom balls and dot surfaces when displaying the Ball amp Stick Cylindrical Bonds or Space Filling models When you generate close contacts go to Structure gt Measurements gt Generate All Close Contacts ChemBio3D 14 0 determines close contacts by comparing the distance between pairs of non bonded atoms to the sum of their van der Waals radii f Note The van der Waals radii specified in the Chem3D Building Atom Types table do not affect the results of an MM2 computation The radii used in MM2 computations are specified in the M
399. y conventions For more information see Attachment point rules on page 26 To use a substructure as an independent fragment make sure no atoms are selected To insert a substructure into a model select the atoms bonded to the substructure attachment points To know how to use substructures to create models see Substructures on page 74 Angles and measurements The measurements between the selected atoms and nearby unselected atoms are saved with the substructure These measurements are used to position the substructure relative to other atoms when it is used in your model For example ChemBio3D stores with the substructure a dihedral angle formed by two atoms in the substructure and two unselected atoms If more than one dihedral angle can be composed from selected substructure and unselected non substructure atoms the dihedral angle that is saved with the substructure consists of the atoms with the lowest serial numbers Consider the following model to define a substructure for alanine Since polypeptides are specified beginning with the N terminal amino acid N 4 should have a lower serial number than the carboxyl C 6 To ensure that a chain of alanine substructures is formed correctly C 1 should have a lower serial number than O 3 so that the C C N C dihedral angle is used to position adjacent substructures within a label Attachment point rules When you save a substructure its attachment points are saved with it C
400. yed according to a widely used color convention derived from amino acid hydrophobicities where the most hydrophobic lipophilic is red and the least hydrophobic lipophobic is blue Partial Charges and Electrostatic Potential derived from the partial charges These properties are taken from the currently selected calculation If you have performed more than one calculation on the model you can specify which calculation to use Go to Surfaces gt Choose Result Isovalues Isovalues are constant values used to generate a surface For each surface property values can be calculated throughout space For example the electrostatic potential is very high near each atom of a molecule and vanishes as you move away from it ChemBio3D generates a surface by connecting all the points in space that have the same value the isovalue Weather maps offer other common examples of isovalues in two dimensions connecting loc ations of equal temperature isotherms or equal pressure isobars There are two isovalues to select from depending on the surface you choose For the total charge density surface set the isocharge value for the molecular orbital sur face set the isocontour value Setting an isovalue To set an isovalue 1 Go to Surfaces gt Choose Surface and select a surface type 2 On the Surfaces menu select either lso gt contour or lso gt charge 3 Adjust the slider to the new isovalue The new isovalue is the middle value listed at the bottom

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