11. Getting Started...

This section describes very quickly the method for setting up a docking using the AutoDock programs. You should find all these utilities under the "share" and "bin" directories.

The macromolecule first needs polar hydrogens to be added and then partial atomic charges to be assigned. This can be done efficiently in SYBYL, e.g. , using the "Biopolymer" menu, adding "Essential_Only" hydrogens and assigning "KOLLUA" partial charges to the protein. Create the PDBQS file 1 for the macromolecule. Save the protein in "mol2" format, and then convert into PDBQS format using " mol2topdbqs ". This also assigns atomic solvation parameters and creates " macro.pdbqs ":

% mol2topdbqs macro.mol2

If you already have a PDBQ-formatted version of your macromolecule, say " macro.pdbq ", you must assign the atomic solvation parameters to it. The " addsol " program will input " macro.pdbq " and output a PDBQS file, " macro.pdbqs ":

% addsol macro.pdbq macro.pdbqs

Create the ligand PDBQ file 2 using "deftors" 3 , to define any torsions that you want to be explored during the docking. (Label the ligand with "Atom ID" or atom serial numbers in a molecular viewer. This will help in assigning the atoms):

% deftors lig.mol2

Create the GPF (grid parameter file) and the DPF (docking parameter file).

% mkgpf3 lig.pdbq macro.pdbqs
% mkdpf3 lig.pdbq macro.pdbqs

These create files with names derived from the ligand and macromolecule files, namely " macro.gpf " and " lig.macro.dpf " 4 .

Edit the GPF and then use AutoGrid to calculate the grid maps.

% autogrid3 -p macro.gpf -l macro.glg &

Edit the DPF and then perform the dockings using AutoDock.

% autodock3 -p lig.macro.dpf -l lig.macro.dlg &

To view docking results in a molecular modelling program, use " get-docked ", to create a PDB formatted file. It will be called " lig.macro.dlg.pdb " and will contain all the docked conformations output by AutoDock in the " lig.macro.dlg " file.

% get-docked lig.macro.dlg

Or to view in AVS, use " mkdlgfld "," mkatmtypfld " and " mkbndfld ".

You don't need to do this step. But if you are interested, you can calculate the energy of a given ligand conformation in the crystal structure you used to calculate the maps:

% autodock3 -p lig.macro.dpf -l lig.macro.epdb.log -c < lig.macro.epdb.com

where the AutoDock command file " lig.macro.epdb.com " contains the two commands, " epdb lig.pdbq " and " stop " on separate lines.

There are several Unix shell scripts and " awk " programs to help set up default parameter files for AutoGrid and AutoDock . They are described in more detail in the Appendix. The user must check their input "gpf" and "dpf" files, to ensure the defaults look reasonable. The user can adjust the default parameters using a text editor like " vi " or " emacs ". These parameters are described in the sections "AutoGrid Parameter File Format" and "AutoDock Parameter File Format", in the appendices.

1. This contains the PDB records in addition to the partial atomic charges and atomic solvation parameters.

2. This contains the root atoms and the branches and torsions defining the rotatable bonds in the ligand, as well as the partial atomic charges.

3. The script deftors uses the program AutoTors to assign root atoms and torsions.

4. The stems differ because the grid parameter file is specific to the macromolecule only, but the docking parameter file is specific to both the ligand and the macromolecule. Therefore, try and keep the ligand and macromol filename stems short.