AutoDock4 Pose Reproduction Tutorial

The purpose of this tutorial is to provide members of the Rizzo lab a way to benchmark the AutoDock4 software to compare the Pose Reproduction success rates against the DOCK6 software. (Note: The program version used for this experiment was AutoDock4.2.6 and DOCK6.9

I. Introduction

AutoDock4 is a commonly used docking program which assess the affinity of a ligand, a drug candidate to a target site (Protein, Enzyme, RNA). To evaluate a software's ability to accurately reproduce experimental results, an experiment called Pose Reproduction was developed

Pose Reproduction used an experimental known ligand and protein complex from the PDB database and attempts to dock this ligand back into it's original location. If the lowest energy ligand(most energetically favorable) is within 2.0 RMSDh of the original target site, this is referred to as a docking success. If any of the ligands, but not the lowest energy ligand is within 2.0 RMSDh of the original target site, this is referred to as a scoring failure. If none of the ligands are within 2.0 RMSDh of the original target site this is referred to as a sampling failure.

II.Prepping Directories

First step is prepare a file with a list of systems within it. For this docking experiment this file was called clean.systems.all

121P
181L
182L
183L 
184L
etc

Second step run the run.000.AutoDock.source.sh script to prepare a directory for each system in the file. The 1st arguement is the list of systems file made in the previous step. The 2nd Arguement is the new directory that will be made where all the AutoDock4 experiments will be performed

bash ./run.000.AutoDock.source.sh ../clean.systems.all AutoDock4_Tutorial

The directory where all the directories will be formed is

AutoDock4_Tutorial/

Each System will have it's own directory in this file

AutoDock4_Tutorial/121P/
AutoDock4_Tutorial/181L/
AutoDock4_Tutorial/182L/
etc

III.Preparing Receptors and Ligands

For this part of the experiment, the receptors and ligands were prepared into pdbqt format. To accomplish this part of the experiment the original mol2 files were used from the testset to convert these systems. The ligands will be assigned gasteiger charges and am1bcc charges will be assigned to the receptor, which produced the highest success rates in previous experiments and was performed in previous papers. Scripts were developed to process these systems from mol2 to pdbqt.

Command to convert these files

Step 1) Make sure you are in the correct directory

cd AutoDock4_Tutorial/

Step 2) Run the correct bash script to run these molecules

bash ./../run001.AutoDock4.system.prep.sh /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/clean.systems.all ../AutoDock4_Tutorial

This script will create a ligand and pdbqt receptor in each system directory

cd 121P/
ls

121P/121P.lig.am1bcc.pdbqt
121P/121P.rec.clean.mol2

Further Processing may be needed to prepare these systems, will explain later

IV.Preparing Grids

For this part of the experiment the grids will be generated for each ligand and receptor