Grid Tutorial

Example: HIV-1 Protease Inhibitor, XK-263

AutoDock requires pre-calculated grid maps, one for each atom type present in the ligand being docked. These maps are calculated by AutoGrid. A grid map consists of a three dimensional lattice of regularly spaced points, surrounding (either entirely or partly) and centered on some region of interest of the macromolecule under study. Typical grid point spacing varies from 0.2Angstrom to 1.0 Angstrom, although the default is 0.375 Angstrom which is roughly one quarter of the length of a carbon-carbon single bond. Each point within the grid map stores the potential energy of a 'probe' atom of the grid map type that is due to all the atoms in the macromolecule. For example, in a carbon map a specific point represents the potential energy of a carbon atom in the ligand at that point in the macromolecule.

This tutorial shows how to use Grid to prepare a parameter file 'xk.gpf' to be used by AutoGrid to build grid maps.

Grid :

Macromolecule

Read Macromolecule

User select a new macromolecule . 'pdbqs', 'pdbq', 'pdb' or 'mol2' types can be used. AutoGrid requires 'pdbqs' type file which has both partial charges and solvent parameters added so charges, polar hydrogens and solvation parameters can be added as needed. There should be no nonpolar hydrogens or lone pairs in the macromolecule so these can be merged. Please note that the atom types in the macromolecule are checked vs a list of standard types: CNOSH. If an unusual atom type is detected in the macromolecule, the user is presented with the option of adding that type which entails changing the name and defining new energy parameters for the new type. Two new types, the first named 'M' and the second 'X', can be accommodated. The result can be saved as a pdbqs file.

Choose Macromolecule

The user may select a molecule which is already present in the viewer.

Merge NonPolar Hydrogens

This command merges nonpolar hydrogens of a selected macromolecule and allows the user to write a corrected pdbq(s) file.

Add Solvent Parameters

This command adds solvent parameters a selected protein which has partial charges and writes a pdbqs file. (NB. solvent parameters are residue based.)

Grid :

Set Map Types

Set Map Types Directly

The types of the maps to be calculated may be entered as a string. Possible types include: CNOPSHfFcbIMZ.

By Choosing Ligand

Map types are set to the set of elements found in the choosen molecule.

By Reading Formatted file

A new molecule is added to the viewer by reading the chosen file. As before, map types are set to the set of elements found in the molecule.

Set Parms For New Atom Type

AutoGrid calculations are based on two sets of parameters: the equilibrium separation distance between the nucleii of two like atoms, 'Rij', and the pairwise potential energy, 'epsij'. Parameters for new atom types may be added to the current session via this menu choice. Also, this menu entry could be used to change default values for the standard types CNOPSHfFcbIM.

Set Up Covalent Map

Parameters for a covalent map can be set with this option. It entails setting the energy barrier height, its half-width, a constant for the Covalent Map and specifying the attachment atom.

Grid :

Set Grid

Setting the extent and center of the maps.

Grid :

Set Other Options

Choosing whether to model hydrogen bonds, whether to generate a floating potential map and what kind of dielectric constant to use

Grid :

Write .gpf ... :

Writing the grid parameter file

Grid :

Edit .gpf ... :

Editting the grid parameter file.

Grid :

Get values from a GPF

This allows the user to read in all the values defined in a previously prepared AutoGrid parameter file (or 'GPF').

ADT

Introduction

Ligand

Grid

Docking

Run

Analyze