5.5 CoMFA Dialogs
5.5.1 Add New CoMFA Column Dialog
Function:
To define how the CoMFA fields in a CoMFA column are to be derived.
License Requirements:
This feature requires a QSAR license ("QSAR").
Menubar:
Dialog Description:
Figure 36 Add New CoMFA Column dialog
Note: The settings in this dialog also affect the form of any Field Fit energy calculations.
CoMFA Field Class [option menu]
Select the class of field you wish to create.
- Tripos Standard Steric and/or electrostatic potentials are evaluated at every lattice point.
Command: TAILOR SET COMFA TRANSFORM NONE
Several options are available to you for transforming the Tripos Standard field if you have an Advanced CoMFA license:
- H-bond
- Paired hydrogen bond acceptor and donor fields are created. Lattice points are assigned an energy of 0 if they are not near H-bond acceptor (or donor) atoms, or if H-bonding interactions are forbidden by steric congestion (i.e., if the steric potential exceeds the steric cutoff). Lattice points in sterically allowed regions which are close to acceptor (or donor) atoms are assigned a nominal energy equal to the designated steric cutoff.
- The criteria for "near" are tailorable: TAILOR SET LEAPFROG H_DONOR_RAD (default 3 Å) for donor fields, and TAILOR SET LEAPFROG H_ACCEP_RAD (default 2.6 Å) for acceptor fields. Lattice points can be H-bond accepting only if they are not H-bond donating.
- See Optional Incremental Hydrogen Bonding Contribution in the LeapFrog Manual and Ref. 13 in the QSAR Background Reading section for further discussion.
- Note: The H-bond acceptor field is subsequently referred to for user-specified scaling and in analysis output as the "steric" component, and the more sparse donor field is identified as the "electrostatic" component. The donor and acceptor fields are not currently separable.
- Indicator
- Steric potentials which fall below the steric cutoff are assigned an energy of 0. Potentials falling at or above the cutoff are assigned a nominal energy equal to the cutoff. This speeds up any subsequent CoMFA PLS calculations and shifts the focus of analysis towards intermediate energies.
- The same logic is used for electrostatic indicator fields, except that it is the absolute value of the potential which is considered, and the indicator generated retains the sign of the original field.
- Note: Basing a PLS analysis on indicator fields is not equivalent to using column filtering.
- Parabolic
- The magnitude of the calculated potential at each lattice point is squared. Electrostatic parabolic fields retain the sign of the original field.
Field Value Settings
Type(s) [option menu]
Select the type(s) of CoMFA fields to be calculated for this column.
- Steric Only the steric field will be calculated.
- Electrostatic Only the electrostatic field will be calculated.
- Both Both the steric and electrostatic fields will be calculated.
Dielectric [option menu]
Select a value to control the form of the Coulombic electrostatic energy calculation.
- Distance energy falls as 1/r2
- Constant energy falls as 1/r, the pure Coulombic expression
Smoothing [option menu]
Select a smoothing value. This option allows the field value used in CoMFA to be an average of actual field values.
- None Uses the actual value as the field value.
- Box Uses as the field value the average of field values at the vertices of a box centered on the actual value.
- Sphere Uses this as the field value, if the Region describes a known receptor, in conjunction with a sphere radius to be specified.
Note: This has no effect unless the Cutoffs Transition is Abrupt.
Drop Electrostatics [option menu]
- Never to include electrostatic field values at points which fall within the molecule, as defined by the steric cutoff energy.
- Within Steric Cutoff for Each Row
the electrostatic field values at points where the steric energy exceeds the steric cutoff for that particular molecule will be set to the mean of any non-excluded electrostatic field values. As a result, sterically excluded points in individual molecules will not contribute to PLS calculations.
- Within Steric Cutoff for Any Row
the electrostatic field values at points where the steric energy exceeds the steric cutoff for any molecule in the analysis will be set to the mean of any non-excluded electrostatic field values. As a result, points within the volume union of all the molecules entering into the analysis will not contribute to PLS calculations.
Cutoff Settings
Steric [field]
Enter a cutoff value. Any steric field value that exceeds this value will be replaced by this field value, thus making a plateau of the steric field close to the center of any atom. For H-bond fields, this cutoff defines lattice points at which H-bonding is sterically precluded and is taken as the nominal energy for non-zero field values. For steric indicator fields, this cutoff also defines the indicator weight.
Electrostatic [field]
Enter a cutoff value. Any electrostatic field value whose absolute value exceeds this value will be replaced by this field value, with the appropriate sign, thus making a plateau of the electrostatic field close to the center of any atom. For electrostatic indicator fields, this cutoff also defines the indicator weight.
Transition [radio button set]
Select the type of transition between the cutoff plateaus for the steric and electrostatic calculations.
- Smooth Interpolates from 6 kcal/mol below the cutoff to the plateau.
- Abrupt Discontinuous.
Note: The transition must be Abrupt for smoothing (Field Values) to have an effect.
Region Settings
Create Automatically [radio button set]
Select this button to create a new region file automatically as part of CoMFA Column creation. It will extend at least 4 Å beyond every molecule in all directions, will have a 2 Å spacing, and a probe atom with vdW properties of c.3 (sp3 carbon) and a charge of +1.
Use Existing Region [radio button]
Click on this button if the Region to be used in field calculation is already described by an existing file.
Filename [field and push button]
If you selected the Region Use Existing radio button, enter the name of the file that describes the region or click on the push button to use the Select File Dialog to identify an existing region file.
Field and Alignment Settings
Define [push button]
Select this button to immediately define a new region file by means of the CoMFA Region Dialog.
Use External Fields [check box]
Check this check box if you wish to associate CoMFA fields calculated externally to SYBYL, for example, fields produced by programs GRID or HINT, with at least some of the molecules under study.
Before the CoMFA field is calculated for any particular molecule within a column, you will be prompted for the name of an external field to be used. If you prefer instead to have a particular CoMFA field calculated in the normal fashion, enter No at the prompt.
Note: Ensure that all fields in external files are based on the same region, or set, of lattice points.
Use Saved Alignments [check box]
Ordinarily, the molecular alignment (= conformation + orientation) used in a CoMFA field calculation is the model currently saved in the database or in the selected Conformer Column.
Check this box if you wish to realign at least some of the saved molecules, before their fields are calculated, by referencing a previously saved alignment. This can include only rigid-body rotations and translations, not conformational changes.
Before the CoMFA field is calculated for any particular molecule within a column, you will be prompted for the name of an alignment to be used. If no special alignment is to be used, enter None at the prompt.
Note: This option is largely superseded by the availability of Conformer Columns.
Additional Information:
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