2018 DOCK tutorial 2 with PDBID 1C87

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For additional Rizzo Lab tutorials see DOCK Tutorials. Use this link Wiki Formatting as a reference for editing the wiki. This tutorial was developed collaboratively by the AMS 536 class of 2018, using DOCK v6.8 and it shows how to dock a ligand into a receptor.

I. Introduction

DOCK

DOCK is a molecular docking program used in drug discovery. It was developed by 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.

1C87

In this tutorial we will use PDB code 1C87, which is the crystal structure of protein tyrosine phosphatase 1B complexed with 2-(oxalyl-amino-4,7-dihydro-5H-thieno[2,3-C]pyran-3-carboxylic acid.

Organizing Directories

We are going to create and organize directories so it would be easier for us to find or identify files in each directory. 

~/gpfs/projects/AMS536/2018/

                                         /001.files/
                                         /002.spheres/
                                         /003.box/
                                         /04.dock/
                                         /05.large-virtual-screen/
                                         /06.virtual-screen/
                                         /07.footprint/
                                         /08.print_fps

II. Preparing the Receptor and Ligand

Download the PDB File (1C87)

We are going to the PDB website (https://www.rcsb.org/) to download 1C87.pdb file and transfer this pdb file to your directory. First, open Chimera and load 1C87.pdb file. Remove the receptor and save ligand (not HOH) in mol2.format. "mol" format shows types of bonds whether it is single or double bond. Then, add H on receptor and ligand by clicking Tools and Structure Editing and save the files. NOTE: when you add H on ligand, make the charge -1. Check the article that is related to pdb file to decide whether it should be pronated or depronated. Lastly, open the receptor file and click Surface Editing and write DMS file. Make sure to save all files. So far, we will have these files ready. 

1c87.pdb             lig_withH_charge_1c87.mol2  noh_receptor_1c87.mol2
lig_withH_1c87.mol2  noh_lig_1c87.mol2           rec_withH_1c87.mol2

After saving these two files with H, transfer files into directory: 

 scp -r ./*1c87* username@login.seawulf.stonybrook.edu:/your_pathway

 vi INSPH.in
/noh_surface_rec.dms
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