2020 DOCK tutorial 2 with PDBID XXXX

I. Introduction

DOCKING

DOCK, a commonly used computational tool used to sample a library of small molecules, ligands and attempts to successfully dock these within their target site, typically a rigid protein into their most energetically favorable positions. To accomplish this, first DOCK uses a global search of the entire protein to determine which locations will be the most energetically favorable, which will be the anchors. Following this, these ligands will take on a variety of different geometric poses to obtain the most conformationally favorable ligand positions. This software is commonly used to perform the hit to lead process in drug discovery to narrow down the drug possibilities from up to hundreds of millions to a few hundred. The drug discovery process then continues using this framework to further select and refine the potential drug candidates.

2GQG

This rigid protein is of the ABL Kinase Domain with the ligand being Dasatinib. This structure was identified using X-ray crystallography with a 2.4A resolution, lower resolutions are preferred.

Directories

For this part of the experiment, create an initial directory in your linux operating systems to work on your experiment

          mkdir 2GQG_Experiment

Following this change the directory to this directory

          cd 2GQG_Experiment

Use the mkdir command in your linux operating system to make all these directories to store your files for the experiment

          00.files
          01.dock_prep
          02.surface_spheres
          03.grid_box
          04.dock
          05.footprint
          06.virtual_screen
          07.virtual_screen_mpi
          08.cartesian_min
          09.rescore

II. Protein and Ligand Preparation

For the first step open up your chimera, go to file and fetch by ID to retrieve the PDB file 2GQG.

The Kinase is dimerized with another kinase to form 2 different chains so delete one of these chains. To produce the resulting image shown in Figure 1.

Check the structure

Read over the information for this protein-ligand complex to determine the charge and environment of the structure to make sure everything is correct. Make sure that there are no issues with the molecules, that aren't physically possible because otherwise they do not accurately represent the experimentally known.

Receptor Preparation

Open up the 2GQG.pdb file, Delete all non standard residues in the structures including the solvent molecules, water and the ligand. To do this task, go in chimera to select->residue->all-nonstd atoms. Following this delete these molecules. Unique features specifically to this receptor, Delete the Phosphorous atom from this file because it isn't close to the docking site and this phosphorous atom is significantly difficult to parameterize. Also swap two of the residues in the protein structure, the PTR residue on residue 172 with TYR and the ARG residue on 164 with another ARG. To swap these residues, change these residue structures