Zap 1.00 Manual: Chapter 5S

Usage and Strategy

Objectives

This chapter describes the basic steps you should follow to use the SYBYL version of Zap. It is mainly an overview of the Zap strategy. Several specific tutorials that cover most of the commonly used features of Zap are featured in the next chapter.

After studying the descriptive material in the Zap Strategy section and performing the later tutorials you should comfortable with the following operations of Zap:

Calculating the solvation energy for small molecules or biomacromolecules.
Calculating atomic potentials (from charges).
Mapping electrostatic potential surfaces.
Using Zap fields and parameters in CoMFA.

Methodology

First we will outline the basic steps involved in a Zap calculation. Commands provided in Zap are discussed in general terms in the order in which they are used in a typical calculation. Also included are suggestions about when certain parameter values should or should not be used. For a more detailed discussion of each command, refer to the Graphical Interface chapter which has a detailed description of each parameter.

Basic Steps for a Zap Calculation

To summarize the basic steps involved in the Zap calculation, the process consists of four steps:

Create and modify the input molecule(s).
Set up calculation parameters.
Run the calculation.
Analyze the results.

Step 1: Defining the Molecule(s)
A Zap calculation can be performed on any molecule that exists in SYBYL. (Some Zap calculations may be run on two molecules simultaneously.) Molecules can be read from files, created within SYBYL, or may be the result of work performed in another SYBYL application module. Note that Zap generally does not modify the molecule(s) in any way. Therefore, any desired modifications, such as adding hydrogens to a molecule read from a PDB file, must be done prior to starting the Zap calculation. As Zap relies on the current SYBYL atomic charges for computations, these must be properly set by whatever charge model you prefer, before initiation of any Zap calculation. In the sections below, the molecule(s) upon which the calculation is performed are referred to as the input molecule(s).
Step 2: Setting up the Zap Calculation Parameters
- Defining the Grid Region
  A crucial part of all Zap calculations involves mapping the molecule or interacting molecules onto a three-dimensional grid. For Zap calculations where the net result is not a map, i.e., for solvation energy calculations, etc., this function of defining the molecular region is handled automatically by Zap, with only some rudimentary user input such as "Calc. Resolution = Low, Medium, High". However, for calculations where the result is a 3D grid, this involves the use of the Region Definition Dialog Box to define this grid. There are three basic quantities that must be specified: the Grid Center, Grid Size, and Grid Resolution.
  The most common method used to define the grid involves specifying the Molecule Extents to be placed in the center of the grid, along with a Margin to surround this region. A special case arises for InterMolecular interaction maps where the best description of the region may be defined in terms of the Interfacial Region (or overlap) and Margin between two molecules. Alternatively the Grid Center may be specified as any arbitrary cartesian coordinate value.
  The selected margin must be sufficient for boundary effects. Typically, a margin in the vicinity of 4-5 Angstrom is sufficient.
  The only quantity left to specify is the Grid Resolution. This is a single value described as the spacing between grid points in Angstroms. It is recommended that a grid resolution of 1.0 Angstroms or less be chosen for the construction of Zap maps.
- Specifying Map Sub-Types
  There are two Grid Map Sub-Types that may be specified during the setup of a ZapMap calculation. These are Molecular Potential and Induced Solvent Charge. The former type maps the electrostatic potential (or energy), while the Induced Solvent Charge 3D map is a display related to solvation energy.
- Iterations and Convergence
  The Zap calculation is iterative, that is, the solution to the Poisson-Boltzmann equation is obtained by successive approximations and calculations until the convergence criteria is met or the maximum number of iterations is exceeded.
- Output File Specification
  Other than some scalar quantities, the main output type of Zap is 3D maps. These are generally written in the Sybyl .cnt" format. However, the Zap program will also write out, if requested, maps in the GRASP ".phi" format. All maps are a collection of scalar quantities, referenced by their coordinates in 3D space surrounding and including the molecule(s) of interest.
Step 3: Performing Zap Calculations
After all the parameters are specified, you are ready to run the Zap calculations. All of the Zap calculations can be run either in Interactive mode or as background jobs through the SYBYL NetBatch utility. The choice of run mode is dependent on the complexity of the calculation, in particular the size of the molecule(s). For small molecules or regions map calculations take on the order of only a few seconds, such that choosing to calculate the map interactively is more convenient and faster than submitting a background job. In contrast, macromlecular calculations may take as long as several minutes and running them "interactively" is more inconvenient.
Step 4: Analyzing the Results
The graphical (map) results of Zap are analyzed by contouring and displaying the 3D maps with the Sybyl tools.
- Molecule and Solvation ZapMaps
  At completion of an Interactive Zap Map calculation a dialog box will appear to assist in contouring the map. (For batch calculations this dialog box can be invoked by selecting the Contour option on the Zap Map submenu.) The positive contours represent regions of the molecule or assembly that have positive potential (and would be attractive to negatively charged ligand fragments) and the negative contours represent regions of the molecule or assembly that have negative potential. The Induced Solvent Charge map can be similarly interpreted.