AutoDock Vina Pose Reproduction Tutorial

I.Introduction

This tutorial is to teach the user how to dock molecules using AutoDock Vina. This tutorial will utilize many of the same scripts and parameters as AutoDock4 to perform these AutoDock Vina experiments. The goal of this experiment is to compare the experimental results to DOCK6 to determine the pros and cons of both the programs

(Important Note: If you already conducted an AutoDock4 experiment previously, you can work in that directory and skip to Part IV,the Docking step)

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 AutoDock Vina experiments will be performed

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

The directory where all the directories will be formed is

AutoDock_Vina_Tutorial/

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

AutoDock_Vina_Tutorial/121P/
AutoDock_Vina_Tutorial/181L/
AutoDock_Vina_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. The charges of these systems aren't a key factor because AutoDock Vina doesn't rely utilize th

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.pdbqt

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

This scripts used to accomplish this were prepare_ligand4.py and prepare_receptor4.py found in mgltools/1.5.6

IV.AutoDock Vina Docking

(Note: You can start here if you finished the AutoDock4 Tutorial already) This part of the project will deal with the docking the molecule properly using a script, that generates a gpf using mgltools, creates the input parameters for docking, then performs all the AutoDock Vina Experiments

The grid parameter file, gpf is generated to determine the center of the ligand which is where the binding site is located, an essential step for this process to work.

Following this, a parameter will file will be generated for each system containing the ligand, receptor, the grid center, and the grid size.

Default grid sizes

receptor=1AGW.rec.clean.pdbqt
ligand=1AGW.lig.am1bcc.pdbqt

center_x=10.354
center_y=3.962
center_z=21.128

size_x=15
size_y=15
size_z=155

out=1AGW_vina.pdbqt

This generates a list a list of 10 different pdbqt files to study

The script will implement a command to split all the AutoDock Vina pdbqt results into multiple pdbqt files

V.Rescoring AutoDock Vina Results

The goal of this section is to convert these results from pdbqt to mol2 formats and rescore these molecules using the DOCK6.9. These are rescored in DOCK6.9 to create a fair scoring method using the Hungarian RMSD scoring method.

1) First step requires these molecules to be converted from pdbqt to mol2 format fir all the systems

1st argument is the number of ligands that were docked in the experiment

2nd argument is the Docking directory were all the Vina experiments were performed

3rd argument is the list of all the systems being converted

bash /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/slaverty_autodock_runs/pdbqt_to_mol2_vina.sh 9 Vina_Tutorial /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/clean.systems.all

2) The next script will proceed to rescore all these molecules with DOCK6.9

1st argument is the docking directory where all the docked experiments were performed

2nd argument is the list of all the systems tested

bash /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/slaverty_autodock_runs/run003.AutoDock_Vina_rescore.v3.sh Vina_Tutorial /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/clean.systems.all

Now all the systems have been rescored with DOCK6.9 and the rescore process is almost complete. One issue when converting these ligands from pdbqt to mol2 is that that the atom types of the original atom and docked molecule are different making it impossible for the DOCK6.9 to properly rescore the molecule and thus outputs a -1000. Typically for about 20-30 systems. To correct for this a script was developed to fix these problematic ligands.

1st argument is the list of all the systems docked in the experiment

2nd argument is the Docking directory of Vina

python /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/slaverty_autodock_runs/atom_type_fix_rescore.py  /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/clean.systems.all Vina_Tutorial

This will fix all the problematic ligands and make a list of all these systems called "redo_rescore.txt". Following this these systems will then all be redocked again with DOCK6.9

bash /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/slaverty_autodock_runs/run003.AutoDock_Vina_rescore.v3.sh Vina_Tutorial /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/slaverty_autodock_runs/AutoDock4_Tutorial/redo_rescore.txt

VI.Analysis Scripts

Lastly 2 scripts will be used to analyze the results, one to generate a csv file and another to graph the results

This script is used to generate the csv file

1st argument is the docking directory of all the results

2nd arguement is the list of all the systems that were docked

3rd argument is the csv file

python /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/slaverty_autodock_runs/AutoDock4_Tutorial/bickel_laverty_calculate_autodock4_results.score.noH.py Vina_Tutorial /gpfs/projects/rizzo/yuchzhou/RCR/DOCK_testset/clean.systems.all AutoDock_Vina_Results

This will generate a csv file in the following format

Using this data analysis scripts will be used to analyze the results by creating these graphs

1st argument is the csv file generated in the previous step

2nd Argument is the type of graph to make(Note: Didn't obtain in time from AutoDock Vina and thus graphs 2 and 3 don't work, Important to obtain time later)

This is the AutoDock Vina results and represents the success rate of all these systems