Exons:
Relevant bits of information for using the MUSC Shared Resource,
 the BioMolecular Computing Resource (BCR).

Exon_24 UCSF DOCK version 4 at MUSC.

1) Go READ the very nice DOCK 
manual BEFORE you tackle this program.

2) Seriously. Get a copy of the Dock4
manual and read it before starting
   any project using Dock4.
   
3) Dock is set up to run with SYBYL as a viewer. Dock has no intrinsic
   GUI and must be run from the UNIX command line. Dock requires
   that the CONNOLLY program be available. CONNOLLY IS available.
   
4) Running Dock v4 at MUSC will require that you add a line to your
   ".cshrc" file. That line should read:

   source /usr/common/bcr/dock4/startupDOCK.csh

   An alternative would be to remember to execute the source command
   manually each time you want to work with Dock4.

5) Using Dock REQUIRES that you create or modify several files in
   a series of preliminary steps outlined in brief in step 6 below 
   and in detail in the DOCK4 manual.

6) What you will need:

  a) Receptor with at least some idea of where the binding site might bind.
     If you have not got a clue, then try some literature searches,
     multiple alignments (looking for conserved residues) of homologs,
     OR run MONTE CARLO RESEARCH with DockVision. To prepare the
     receptor file for Dock, remove all crystallization waters. Fix atom 
     types and bonding for any cofactors, rename CYS and HIS residues 
     according to Dock Manual Suggestions. Add charges. Create an 
     "exclude.pdb" file. The exclude.pdb file will be the receptor MINUS 
     those regions where you think binding might occur.

  b) A Ligand or database of ligands, in SYBYL MOL2 format with atom types
     and bond orders properly assigned.

  c) A molecular surface calculated by the Connolly algorithm. The Connolly
     program aka MS is installed for your use but there are some things you will
     need to do first. You will need copies of two REQUIRED data input files 
     called file1.dat 
     and  file2.dat. These two files may be copied from the
     indicated hyperlinks. In addition you will need a specially formatted
     copy of your receptor. The DOCK4 package has a utility which will convert
     standard PDB files into a proper Connolly format. This utility is called
     "pdb2ms" and it is ready to run as well (after you source the csh file
     in step 3). Finally the Connolly output file called "CONTACT" will need
     to be converted into a Dock4 usable format. The DOCK4 utility called
     "reformatms" will convert Connolly CONTACT into a DOCK4 format. REFORMATMS
     is an interactive program. 
              1. - Convert your receptor PDB format file to Connolly format.
                 - Copy the receptor PDB file to a file named "fort.1".
                 - Copy the Exclude PDB file to "fort.2".
                 - Type "pdb2ms" and look in a file named fort.3 for the 
                 output. This output file will be the properly formatted 
                 input file for the Connolly program.
              2. Running Connolly
                 - type "connolly file1.dat file2.dat fort.3"
                   where "fort.3" comes from pdb2ms.
                 -The molecular contact surface will be in a file
                  called "CONTACT"
              3. Run reformatms
                 - type "reformatms". This program asks you for its needed
                   input. The output is a Dock4 formatted molecular surface
                   which is used by SPHGEN in step d.
     
     Finally, there is an automatted script for producing a Connolly surface.
     All the steps of the previous paragraph are coalesced into a single DOCK4 
     utility is called autoMS.

  d) With the Dock4 formatted MS in hand, you then run the Dock4 program
     called SPHGEN which will be used to match the ligand to the  receptor.
     SPHGEN requires an INPUT file called INSPH to be prepared by hand.
     Be sure to remove any old OUTSPH files prior to running SPHGEN.

     Here's a sample INSPH file:

     cAPK_MSDOCK4.ms
     R
     X
     0.0
     4.0
     1.4
     cAPK_MSDOCK4.sph
     
     See the Dock4 manual for details.

  e) You will need a grid box around your receptor region. SHOWBOX does this 
     for you. SHOWBOX will want to know the cluster number. Look in the 
     OUTSPH file for this number.

  f) When you have a finished MS, SPHGEN, constructed your exclude.pdb file
     and examined the sphere site points with SHOWBOX you are ready to run
     the DOCK4 program GRID to construct the actual scoring grid. GRID 
     begins with a nice interactive series of menus where you create a GRID
     input file prior to creating the GRID proper.
     
     Unfortunantly there is a UNIX utility called " grid". Therefore
     you must include the path to the DOCK4 grid in order to select
     it.
     
     /usr/common/bcr/dock4/bin/grid -i grid.in

     The file "grid.in" need not exist prior to running grid.

  g) Finally, with the sphere points, a scoring grid, and a MOL2 format
     ligand, and your receptor, you can run the dock routine itself.
7) Running dock once the  preparation is complete requires just one line:

     dock -i dock.in
   
   The file "dock.in" need not exist prior to running the program. Start up
   includes an interactive menu which prompts the user for required information.


     
 

The BCR at the Medical University of South Carolina
URL: http://bcr.musc.edu/
Last modified: December 5, 2001- ESH

e-mail to Starr comments about this page.