AutoDock Intranet

Setting up the Protein and Ligand for AutoDock

Download PDB Structure

You can obtain the complex's structure directly from the Brookhaven Protein Data Bank, using PDBBrowse. Note: some accession codes have been superseded, as indicated in the superseding PDB file by the new PDB record "SPRSDE", so it is a good idea to search with the ID set to the 3-letters of the desired accession code. Use the "Send entire text" option in the returned page, and then use the browser's "File:Save As..." option to save the PDB file, using the "Format for Saved Document:" as "Text".

If you have your browser set up to launch RasMol (which you should!), you can also take a look at the protein. Try using the "Colours:Chain" option, to see what the different chains are and where any ligands or heteroatoms are.

Split Chains and Heteroatoms

Use the Unix script called "getready" to extract an information file, with the extension ".info", and split the PDB file by chain ID, as in this example:

% getready 4tmn.pdb

This script uses Mike Pique's Unix scripts pdbsplitchains, pdbwaters and pdbdewater. The getready script splits each chain found into A_wat.pdb and A_nwa.pdb, and the non-waters into A_het.pdb and A_atm.pdb files. You need to check that the files called A_het.pdb, B_het.pdb, etc. do not contain more than just the ligand: sometimes they also contain cofactors and metal ions. If this is the case, edit out the the different parts and treat them appropriately. If there are cofactors and metal ions, then in almost all cases, the resulting PDBQ files need to be appended on to the protein PDBQ.

Sybyl: Add Essential Hydrogens and Partial Charges to Protein

This lists the commands to be used in Sybyl's command line interface, to colo(u)r the molecule by atom type, add polar hydrogens, edit the N and C- termini to be charged, and then load Kollman united-atom partial atomic charges. Use the mouse to highlight the commands you want to use, then at the "Sybyl>" prompt click the middle mouse button to paste the text into the Sybyl commands window.

BIOPOLYMER BROOKHAVEN IN M1 \
/tmp_mnt/nfs/eve/export/eve6/gmm/desolv/dir/A_atm.pdb NO
COLOR TYPE M1
BIOPOLYMER ADDH M1(*) ESSENTIAL_ONLY
BIOPOLYMER FIX_END_GROUPS M1 CHARGED
BIOPOLYMER LOAD CHARGES M1(*) KOLL_UNI

Then save the protein using Sybyl "mol2" format.

Convert the Protein into PDBQ-format

Use the script "mol2cnv" to convert into PDBQ format, for example:

% mol2cnv A_atm.mol2

This script actually converts from Sybyl mol2 to PDBQ, sorts on residue number, sums partial atomic charges in residues and checks for non-integer residue charges, and writes out REMARKS informing the user of the total charges and any errors.

Sybyl: Add all Hydrogens to Ligand and Compute Gasteiger Charges

These Sybyl commands will read in the ligand in PDB format, colo(u)r the atom type, add all hydrogens and then compute Gasteiger partial atomic charges. It will also modify the atom names of the newly added hydrogens in a sequential fashion, i.e. H1, H2, etc. This is vital for AutoTors to correctly identify non-polar hydrogens for uniting. Note that you need to check the bond orders and the hybridization of the atoms, for Sybyl to add hydrogens correctly.

BIOPOLYMER BROOKHAVEN IN M1 \
/tmp_mnt/nfs/eve/export/eve6/gmm/desolv/dir/ligand.pdb NO
COLOR TYPE M1

At this point you may have a collection of atoms that are unbonded. This can be fixed either manually, or automatically using "Build/Edit:Crystals..." on M1 and using the "CRYSIN command" "CONNECT" on all atoms, using the "NO_SYMMETRY_SEARCH" and the "DISTANCE_CRITERION" with the default bond distances. This should fix most bonds; if you use a maximum distance of 1.80Å; instead of 1.65Å; this may may form spurious bonds; delete any such erroneous bonds.

Once all the atoms are properly bonded, it will be necessary to define the atom types for most if not all atoms. Use "Build/Edit:Modify:Atom...:ONLY_TYPE" on all the set of "UNK_ATOMS", or unknown atoms; as each atom is highlighted, pick or type in the correct atom type.

FILLVALENCE M1(*) H
MODIFY ATOM NAME M1((<H>+<H.spc>+<H.t3p>)) SEQUENTIAL_AUTO
CHARGE "M1" COMPUTE GASTEIGER 
CHARGE "M1" DISPLAY
LABEL ID M1(*)
UNDISPLAY M1((<H>+<H.spc>+<H.t3p>))

Finally, save the ligand as a Sybyl "mol2" formatted file, then run the script "deftors" to define any torsions in the ligand. Keep the ligand visible in Sybyl, so you can see the atom serial IDs, to help in the dialogue with AutoTors. Use deftors on the ligand mol2 file written out by Sybyl:

% deftors lig.mol2

This will launch AutoTors, and you will be prompted as usual for the root atoms and which torsions to allow to rotate.