The Graphical Interface


Zap and ZapHVMenubar

Found as Zap under "eslc". There are two Zap license levels, called Zap (basic) and ZapHV (high voltage, which is a superset of the basic version). Each has its own specific set of enabled commands. The (basic) Zap command set allows you to calculate Atom Potentials & Energies (from atomic charges), 3D Potential Energy Maps, and calculate molecular solvation energy. The ZapHV license enables additional tools to calculate 3D solvation energy maps, ligand binding energies, residue pKa predictions and a variety of surface and volume electrostatic descriptors. These commands are arrayed in a variety of Zap submenus which will be described in turn in this chapter. In addition there is a ZapQSAR submenu that contains some useful utilities for applying Zap to the SYBYL Molecular Spreadsheet.


Atom Potentials & Energies...

This submenu activates a single command, to calculate and display in the Sybyl graphics window the Atomic Potentials & Energies. Note that this permanently replaces the atomic charges for the molecule, so it would be prudent to save the molecule to disk prior to executing this command. These energies are calculated by solution of the Poisson-Boltzmann equation for the molecule and its dielectric environment. The current atomic charges are used in the calculation, and the result will be dependent on the quality of these.

Zap Atom Potentials & Energies Dialog Box

The Zap Atom Potentials & Energies Dialog Box defines the setup of the calculation for a molecule that is currently displayed in SYBYL. The sub-dialog Zap Details contains options that need to be adjusted less commonly.

Dialog View View Zap Molecule Potentials Dialog Box

Zap Details Dialog Box

The Zap Details Dialog Box assists in defining several less commonly adjusted Zap setup parameters. These are generally associated with Dielectric Model selection and the details of Zap convergence.

Dialog View View Zap Details Dialog Box


Molecular Energies & Properties

This submenu activates three commands: to calculate the solvation energy (induced solvent charge) for a currently active Sybyl molecule, to calculate the binding energy for a ligand/target complex, and to produce a report of electrostatic properties and decriptors for a currently active Sybyl molecule. It is necessary, as in all Zap calculations, for the molecule to have Valid charges.

Zap Molecular Solvation Energy Dialog Box

The Molecular Solvation Energy Dialog Box defines/sets up the parameters for the calculation.

Dialog View View Zap Molecular Solvation Energy Dialog Box

ZapHV Electrostatic Binding Energy Dialog Box

The Electrostatic Binding Energy Dialog Box defines/sets up the parameters and molecule(s) for the calculation.

Dialog View View Zap Electrostatic Binding Energy Dialog Box

ZapHV Electrostatic Structure Report Dialog Box

The Electrostatic Structure Report gives an output text file of a selection of electrostatically-relevant features. This Dialog Box defines/sets up the parameters for the calculation.

Dialog View View Zap Electrostatic Structure Report Dialog Box


ZapMaps

Zap Map Molecule Dialog Box

The Zap Map Molecule is an electrostatic potential map of the molecular region. This dialog box aids in setting up the region for the map and important parameters for the calculation. It is necessary, as in all Zap calculations, for the molecule to have Valid charges. At the completion of the calculation, you will be given an opportunity to contour the map for display within Sybyl.

Dialog View View Zap Map Molecule Dialog Box

ZapHV Map Induced Solvent Charge Dialog Box

The Zap Map Induced Solvent Charge is an electrostatic potential map of solvation energy in the molecular region. This dialog box aids in setting up the region for the map and important parameters for the calculation. It is necessary, as in all Zap calculations, for the molecule to have Valid charges. At the completion of the calculation, you will be given an opportunity to contour the map for display within Sybyl.

Dialog View View Zap Map Induced Solvent Charge Dialog Box

Map Difference Dialog Box

The Map Difference Dialog Box enables you to calculate the difference (or sum) of two separate Zap (or other) contour files. The Difference between two Zap maps for two related molecules can be used to determine the areas where there is significant difference in potential, etc. Note that the validity and interpretability of a map difference result is enhanced when the two input maps match closely in terms of region spanned and grid spacing.

Dialog View View Map Difference Dialog Box

Contour Dialog Box

The Map Contour Dialog Box is a convenience utility for contouring and displaying SYBYL (.cnt) contour files.

Dialog View View Map Contour Dialog Box

Region Definition Dialog Box

The Region Definition Dialog Box assists in describing the region in 3D cartesian space that the map calculation should span.

Dialog View View Region Definition Dialog Box


Zap QSAR

The Zap QSAR submenu contains some utility functions to aid in the use of Zap with the SYBYL QSAR module. Most of the Zap QSAR functionality is associated with the SYBYL Molecular Spreadsheet. This will be discussed in the next section.

The two options available in the ZapQSAR submenu are Graph ZapQSAR... and Fill MSS Cells with ZapCoMFA Field.

Fill MSS Cells with ZapCoMFA Field Dialog Box

This command allows you to fill specified MSS cells with a ZapCoMFA field. You may wish to use this option if you are attempting to predict activity of a new compound with a CoMFA model that includes a Zap field.

Dialog View View Fill MSS Cells with ZapCoMFA Field Dialog Box

Retrieve ZapQSAR Dialog Box

The Retrieve ZapQSAR Dialog Box is a convenience function to facilitate creation (for graphing) of the CoMFA coefficients*standard deviation contour maps for PLS runs where a Zap potential field was included. The dialog box enables selection of the desired field information and writes the selected CoMFA fields to scratch disk files. Then these fields are sequentially contoured.

Dialog View View Retrieve ZapQSAR Dialog Box


Zap and the Molecular Spreadsheet

Zap provides added functionality to the molecular spreadsheet. Three additional column types are defined by Zap/ZapHV: ZAPSOLVATION, ZAPDESCRIPTORS and ZAPCOMFA. These are available through the Spreadsheet "Autofill" button in the list of column types. Note: Occasionally the ZAPCOMFA column type is dropped by the Autofill menu. If this happens, type mss!reset_eslc to the Sybyl> prompt.

ZAPSOLVATION: Add Column (ZapSolvation) Dialog Box

The Add Column (ZapSolvation) Dialog Box sets the parameters for filling the cells in a spreadsheet column with the solvation energy of each molecule (row) in the table.

Dialog View View Add Column (ZapSolvation) Dialog Box

ZAPCOMFA: Add Column (ZapCoMFA) Dialog Box

The Add Column (ZapCoMFA) Dialog Box sets the parameters for filling each cell in a spreadsheet with a Zap Potential or Energy field. This Dialog Box contains parameters related to the Zap calculation for each molecule and parameters related to the map creation for each molecule (row) in the table.

Dialog View View Add Column (ZapCoMFA) Dialog Box

Calculate CoMFA Region Automatically Dialog Box

This dialog box is called from the Zap COMFA routine and is used to set the parameters for defining the CoMFA region based on the union space spanned by the entire molecule set. The routine determines the spatial extents of each molecule and creates a region that encompasses all molecules.

Dialog View View Calculate CoMFA Region Automatically Dialog Box

Define CoMFA Region Dialog Box

The Define CoMFA Region Dialog Box is used if the cartesian coordinate set defining the region (Lower Box Corner, Upper Box Corner) is known, or if a custom region that includes more than one Box is needed. This latter case may be a useful option for some CoMFA experiments where much of the molecular structures are identical and a "closeup" on the areas of difference is appropriate.

Dialog View View Define CoMFA Region Dialog Box

ZAPDESCRIPTORS: Add Column (ZapDescriptors) Dialog Box

The Add Column (ZapDescriptors) Dialog Box sets the parameters for filling the cells in a spreadsheet column with a variety of Zap Electrostatic Structure Descriptors for each molecule (row) in the table.

Dialog View View Add Column (ZapDescriptors) Dialog Box