Docking with AutoDock

Molecular Docking III

Docking requires a structure file for the protein and one for the ligand, both in Protein DataBank format. Presumably, you will have downloaded the protein from the PDB, so it will be in the right format. However, you should look at the file using vi under Linux, or TextPad on the PC. Check:

Make a note of whether water is present, so it can be removed
Similarly note other solvent molecules or ions that are not part of the protein; write down the abbreviations used.

Your file should contain a single functional unit of the protein. Many proteins crystallize as dimers, trimers, and so on. You should remove the additional structures.

In PDB files, separate chains are labeled A, B, C, etc. Generally you will want to keep the A chain and any ligands that are labeled as belonging to the A chain.
If you have any question about what comprises the functional unit, consult the reference cited in the heading of the file. Sometimes one functional unit includes more than one chain.
Note any metals or cofactors that are present; for example, a redox enzyme may contain a heme or NADH.

In other words, be familiar with your enzyme!

Structure files in pdb format for your ligand can be generated using PCModel or Spartan.

In PCModel, draw and minimize the structure in the usual way. Then choose "Save" from the File menu, and scroll down the list of file types in the popup window to "pdb". Choose it, and save.

Likewise in Spartan, build and minimize your structure. Then choose "Export" from the File menu, select "pdb" as the file type, and save.
A graphical interface for AutoDock is available, called Autodock Tools (ADT). It facilitates setting up the input files and the search grid, and has tools for analyzing results. The tutorial is designed to use ADT.
Set up your computer
On our Linux computers, you must edit your .bashrc file (note the period at the beginning!) to provide you access to the docking programs and tools. Load .bashrc into vi or your favorite editor and at the end of the file add the lines:

# Autodock and Autodock Tools
source /usr/local/MGLTools-1.5.4/bin/mglenv.sh
alias adt="/usr/local/MGLTools-1.5.4/bin/adt"
alias pmv="/usr/local/MGLTools-1.5.4/bin/pmv"
alias autogrid="/usr/local/Autodock/autogrid4"
alias autodock="/usr/local/Autodock/autodock4"

Line 1 is a comment that identifies the purpose of the following lines.
Line 2 sets environment variables and allocates memory.
Line 3 aliases AutoDock Tools
Line 4 aliases the Python Molecular Viewer, a standalone biomolecule display program
Lines 4 and 5 alias the component programs of Autodock. You could eliminate these by adding "/usr/local/Autodock" to your Path variable.
Save the file. Then type at the prompt:
source .bashrc
This causes the bash shell to reread its configuration file, which normally is read only at login. Alternatively, log out and log back in.
You can now start AutoDock Tools by typing: adt

This page last modified 2:17 PM on Wednesday August 18th, 2010.
Webmaster, Department of Chemistry, University of Maine, Orono, ME 04469