DOCK 3.5 Score in DOCK6

Author: Kaushik Raha
Last updated September 27, 2008

This tutorial introduces DOCK 3.5 Score in DOCK6 and describes the preparation of input files for and grids for using DOCK 3.5 scoring functions in DOCK6. These techniques should be applicable to any protein-ligand system. 

What is DOCK 3.5 score?

DOCK3.5 score is a variant of Grid-based scoring (see Grid). It is the scoring function available in the dock3.3.54 distributed by the Shoichet Laboratory. DOCK3.5 scoring function calculates ligand desolvation in addition to steric and electrostatic interactions between the ligand and receptor. The electrostatic interactions between the ligand and the protein are calculated from a electrostatic potential (ESP) map. The ESP map is calculated using finite difference Poisson-Boltzmann equation (PBE) as implemented in the program DelPhi. DelPhi is not a part of the DOCK6 distribution. Ligand desolvation is calculated as a sum of the atomic desolvation weighted by a normalization factor that accounts for the extent to which the ligand atom is buried by the binding site. Please see the DOCK6 manual for futher details. In the DOCK scoring hierarchy DOCK3.5 Score follows GridScore and can be used both as the primary and the secondary scoring function.

Input files preparation.

1) Ligand Preparation: The ligand desolvation calculation in DOCK3.5 scoring requires calculation of partial atomic desolvation for the ligand atoms. The program AMSOL is used for this purpose, however AMSOL is not a part of the DOCK6 distribution. If the user has access to AMSOL then ligand preparation scripts can be obtained from us. A ligand preparation page has been setup as a part of ZINC for this purpose as well. 

2) Receptor Preparation:

(a) Clean the PDB file:

Run DOCK6 with DOCK3.5 Score.

USAGE: dock6 -i input_file [-o output_file] [-v]
dock6 -i dock.in > dock.out &

Download a copy of the dock.out file. Check it with your output file to see whether you get any different results.

You can now change the options in the dock.in file, such as increase the number of steps of the amber_score minimization cycles and/or amber_score_md_steps, or increase/decrease the amber_score_temperature, change the amber_score_movable_region, and rerun the calculation to see the change in results.

In general, the best type of movable region could be highly sensitive to the receptor. For example, if specific changes to the receptor upon ligand binding are expected then the NAB_ATOM_EXPRESSION movable region is appropriate. On the other hand, if a little relaxation of the receptor upon ligand binding is all that is desired then a small DISTANCE movable region might be sufficient.

The amount of minimization and MD is dependent on the preparation of the receptor. If the receptor has been well equilibrated then it is expected that fewer min steps and md cycles will be needed to relax the complex, in general. Other factors, such as the type and extent of changes upon binding, are also relevant.