HOW TO RUN DOCK4.0

Read the manual

Do NOT rely on the old habit of "If everthing else fails, read the manual".

www.cmpharm.ucsf.edu/kuntz/dock4/html/Manual.html

Checklist

1. Check your PDB

www.bmsc.washington.edu/people/verlinde/PROTOCOL_PDBforDOCKING.html

2. Remove ligands and water molecules from PDB

3. If your protein is multimeric, renumber the residues

DOCK's administration gets confused if the same residue number is used more than once. However, in most PDB's of multimeric proteins equivalent residues in the different monomers carry the same residue number.

Renumbering is easy with the DOCK accessory program pdbrenum.

4. Calculate the Connolly surface, also called molecular surface, of the protein

At UCSF the Connolly program MSCON is integrated in MIDAS. However, at BMSC we do not have MIDAS. Instead you should use a local program to prepare your PDB for running MSCON. Both the preparation program and MSCON can be launched by the program connolly.

You will see the following menu:

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
~            MSCON PROGRAM by Michael Connolly ~ 
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 

WARNING: This implementation handles only protein 
  0 => short introduction 
  1 => prepare input files 
  2 => calculate molecular surface 
  3 => calculate accessible surface 
  4=> run the surface analysis program 
  5 => run the surface selection program 
 99 => exit this menu 

     What do you want: 

Select option 1.

Check for error messages (I am not kidding) and correct the problem. Usually, the problem is a non-recognized protein atom label.

Select option 2, and opt for 3 dots/A².

This will give you the surface of the ENTIRE protein. Next step is to extract the surface that describes the binding site, which requires several operations:

Run the DOCK accessory program get_near_res to identify all residues within a certain distance of a ligand or a central residue in the docking environment (a PDB file of that residue will be needed).Then, reformat the output of get_near_res with the DOCK accessory program condense. Now, we are ready to extract the binding site dots from the protein connolly surface.

Launch again connolly, and select option 5.

Finally, the extracted surface has to be reformatted with the DOCK accessory program reformatms.

5. Run SPHGEN

6. Analyze the sphere description of the binding site

7. Calculate scoring grids

Before calculating the scoring grids it is imperative that you supplement the PDB coordinates with hydrogen atoms.

This can be done with the DOCK accessory program addprh. Afterwards it may be necessary to do some editing because this program adds hydrogens to all Cys regardless whether they occur in disulfide bonds or not. It also adds hydrogens to both nitrogen atoms in His side chains. Therefore, edit out the unwanted hydrogens after running this program. Subsequently, it is mandatory to reformat the protein in mol2 format. Alas, since we do not have SYBYL it is not trivial to perform this reformatting.

Alternatively, the MSI software insightII can be used to supplement hydrogens. This option makes it also easier to obtain the protein file in mol2 format, which is reqiured for runnig DOCK4.0.

8. Run DOCK