2019 DOCK tutorial 1 with PDBID 2BXF

This tutorial contains a step by step approach to dock a known ligand to a known receptor.

I. Introduction

DOCK

DOCK is a molecular docking program used in drug discovery and molecular modeling. It was developed at UCSF by Dr. Irwin D. Kuntz, Jr. and colleagues at UCSF (see UCSF DOCK). This program, given a protein binding site and a small molecule, tries to predict the correct binding mode of the small molecule in the binding site, and the associated binding energy. Small molecules with highly favorable binding energies could be new drug leads. This makes DOCK a valuable drug discovery tool. DOCK is typically used to screen massive libraries of millions of compounds against a protein to isolate potential drug leads. These leads are then further studied, and could eventually result in a new, marketable drug. DOCK works well as a screening procedure for generating leads, but is not currently as useful for optimization of those leads.

DOCK 6 uses an incremental construction algorithm called anchor and grow. It is described by a three-step process:

1. Rigid portion of ligand (anchor) is docked by geometric methods.
2. Non-rigid segments added in layers; energy minimized.
3. The resulting configurations are 'pruned' and energy re-minimized, yielding the docked configurations.

2NNQ

The tutorial will be based on the PDB file 2NNQ downloaded from the PDB Database. 2NNQ is the crystal structure for a human adipocyte fatty acid binding protein in complex with ((2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)-3-biphenylyl)oxy)acetic acid.

Organization of Directories

Maintaining a clearly organized set of folders will be helpful in finding specific files, calling different files in input files and most importantly keeping track of everything you do. We would like to recommend to maintain the following set of files throughout the tutorial.

             0.files
             1.dockprep
             2.surface_spheres
             3.gridbox
             4.dock
             5.
             6.footprint
             7.virtual_screen
             8.virtual_screen_mpi
             9.cartesianmin
             10.rescore