The Inercial Blog

Preparing the Receptor Files for Molecular Docking

Jun 1, 2023

Introduction

What follows are notes for preparing a receptor from a PDB file for Autodock Vina, a program used to simulate molecular docking between a receptor and a ligand. The receptor preparation described is done here to be compatible with Autodock Vina in Virtual Flow.

The following is required for a receptor used for Autodock Vina:

  1. pdbqt file format
  2. config.txt text file with the docking receptor grid coordinates, assuming the docking is not blind

Tools Installation

This install is on linux machine running Ubuntu 22.04. Note that the latest version of MGLTools doesn’t work on the latest versions of Mac OS (e.g. Ventura).

  1. Download the latest MGLtools tools for Linux on the Scripps CCSB site (as of this writing the latest version was 1.5.7p1)

  2. Extract the tar file into a folder (e.g. applications) run install:

     cd ~/applications
 tar -xvf mgltools_x86_64Linux2_1.5.7p1.tar.gz
 bash install

  3. Source the file (or add it to your .bashrc):

     source ~/applications/mgtools/initMGLtools.sh

  4. Launch Autodock Tools:

     adt

Preparing the molecule

  1. Delete the water molecules:
    • Edit->Delete Water
  2. Remove other heteromolecules (if present)
  3. Repair the missing atoms in the molecule (if missing):
    • Edit->Misc->Check for Missing Atoms
    • Select all the residues, and click Dimiss
  4. Repair the missing atoms (which may take a while):
    • Edit->Misc->Repair Missing Atoms

  5. Under the “S” column, click the circle to deselect the chain

  6. Add Hydrogens:
    • Edit->Hydrogens->Add
    • Select “Polar Only” hydrogens

  7. Add Kollman charges (note that gasteigel charges are only for the ligand molecule):

    • Edit->Charges->Add Kollman Charge
    • Edit->Charges->Check Totals on Residue
    • Click “Spread Charge Deficit over all atoms in residue”
    • Edit->Charges->Check Totals on Residue
    • Verify “no residues with non-integral charges found” message is shown
  8. Add the AD4 type:
    • Edit->Atoms->Assign AD4 type
  9. Save as pdbqt:
    • File -> Save -> Write PDBQT -> OK
  10. Open the PDBQT file and remove “CONNECT” lines, if present

Preparing the config.txt file

  1. Determine the X,Y,Z coordinates of the “center” of your binding site in the PDB file. For example if this Lysine atom is at the center of your binding site:

     ATOM    589  CG  LYS D  41      22.546 -10.869  -2.575

    The X,Y,Z coordinates would be 22.546, -10.869, -2.575, respectively

  2. In Autodock Tools, draw the grid:
    • Grid->Grid Box
  3. Change angstroms to 0.5
  4. Enter the X,Y,Z coordinates from (1)
  5. Expand or shrink the grid box as needed to fill the targeted binding area (e.g. change default 40 to 50)

  6. Copy the numerical values to a config.txt file. For example:

     receptor = ../input-files/receptor/2iyb.pdbqt
 center_x = 22.546  
 center_y = -10.869
 center_z = -2.575
 size_x = 50.0
 size_y = 50.0
 size_z = 50.0
 exhaustiveness = 8
 cpu = 1

Sources