Autodock 4 - overview & preparing ligand & protein

I need to try some dockings of ligands to a protein that will remain nameless until we publish the paper fairly shortly. Essentially I have solved a number of crystal structures and want to design some new compounds but would like an idea of how they bind before the chemists go ahead and make them. I could dock them by eye using a program like COOT or PyMOL, but find it very difficult trying to get all the distances and angles correct. I am not really interested in the calculated delta G's as AutoDock is notoriously bad at estimating these. If I can get a rough ranking that would be great, but otherwise it is the structural detail I am more interested in.

The first thing I did was get my IT manager to install Autodock 4, AutoGrid and AutoDockTools (ADT).

I then performed five steps (I'll talk about 1 & 2 in this post and 3-5 in later posts):

1. Prepare the protein both as a rigid docking receptor and using the new "flexible residues" feature to see if that makes a difference.
2. Prepare the ligands for auto-docking.
3. Make the grid parameter file (.gpf) based on the atoms in the ligands and run AutoGrid.
4. Make the docking parameter file (.dpf) and run AutoDock for each of my ligands.
5. Analyse the results.

For step 1 I used the tutorial: "Using AutoDock 4 with AutoDockTools: A Tutorial" by Ruth Huey and Garrett Morris.

However for step 2 I borrowed some ideas from the virtual screening tutorial as I had twelve ligands to prepare:

1. Firstly I made pdb files of all my ligands using the PRODRG2 server.

2. Next I invoked the file "prepare_ligand4.py" from the ADT utilities24 directory using a c-shell script adapted from the virtual screening tutorial called make_pdbqt.csh and chmod +x'ed:

#!/bin/csh
foreach f (`ls *`)
echo $f
/home/progs/MGLTools-1.5.1/MGLToolsPckgs/AutoDockTools/Utilities24/prepare_ligand4.py -l $f -d ligand_dict.py
end

This produced a bunch of pdbqt files (pdb + partial charges + AutoDock atom types) for each of my ligands.

3. I then "examined" the pdbqt files to get a list of atoms in all the ligands using examine_ligand_dict.py again from the ADT utilities directory, which I copied into my working directory and invoked with the command:

./examine_ligand_dict.py > summary.txt