Pose Reproduction SB2024 V1 DOCK6.10 A

!!!!!!Under Construction!!!!!!

The purpose of this tutorial is to develop a uniform method to test pose reproduction across the Rizzo lab with the DOCK software. Note any data in this tutorial is solely for the purpose of example.

I.Introduction

-Pose reproduction is an experiment which tests a docking programs ability to predict the bound pose of a ligand to a receptor (typically a protein). An experimental structure of a protein-ligand complex is converted into 2 separate files, 1 for ligand and 1 for receptor. The docking program then predicts the binding orientation that is most energetically favorable. In the case of DOCK6, the ligand is flexibly docked with the Anchor & Grow algorithm to a rigid receptor.

-The RMSD between the docked poses and experimental pose are measured. We consider RMSD < 2 angstroms an accurate prediction. There are 3 outcomes we classify.

1) Success - The best scoring pose is < 2 angstroms

2) Scoring Fail - A pose < 2 angstroms was sampled but did not score best

3) Sampling Fail - No pose < 2 angstroms was sampled

II.Necessary files

Scripts to run Pose Reproduction in batch mode are found at:

    https://github.com/rizzolab/Benchmarking_and_Validation

This tutorial uses Single Grid Energy as the primary score for docking. This is the typical score used by the Rizzo Lab for this purpose and for generating poses in Virtual Screening. Thus, grid files are required. The receptor mol2 is only necessary for visualization purposes. The list of necessary files are:

    ${pdb_id}.lig.am1bcc.mol2
    ${pdb_id}.rec.clust.close.sph
    ${pdb_id}.rec.clean.mol2
    ${pdb_id}.rec.bmp
    ${pdb_id}.rec.nrg

All necessary files for different versions of our test set are available for download at:

    https://ringo.ams.stonybrook.edu/index.php/Rizzo_Lab_Downloads

To (re)create a testset using Rizzo Lab Protocols:

    https://ringo.ams.stonybrook.edu/index.php/Test_Set_Tutorial_V1

III.Docking molecules

In 001.submit_dock.sh edit the following variables:

     system_file="List of PDB codes in a file delimited by line"
     testset="Path to necessary files for docking (section above)"
     dock_dir="Uppermost directory of DOCK6 executable"

Additionally other variables can be changed in 001.submit_dock.sh :

    condition="Unique name given to each experiment output - otherwise 'Default' "
    seed="Random seed - otherwise '0' "

A separate dock input file is written for each system.

IV.Pose Reproduction Analysis

-SEE README FILE IN GIT REPO FOR ADDTIONAL DETAILS THAT MAY NOT BE COVERED HERE

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Tutorial Written By: Christopher Corbo, Rizzo Lab, Stony Brook University (2024)

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