Difference between revisions of "DOCK 3.7 tutorial based on Webinar 2017/06/28"

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Scenario 1:  
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= Scenario 1: =
 
Use docking to predicted how Erlotinib (an approved drug) binds to the Epidermal Growth Factor Receptor
 
Use docking to predicted how Erlotinib (an approved drug) binds to the Epidermal Growth Factor Receptor
  
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   -rw-r--r--. 1 tbalius bks    1653 Jun 17 12:27 vdw.parms.amb.mindock
 
   -rw-r--r--. 1 tbalius bks    1653 Jun 17 12:27 vdw.parms.amb.mindock
 
   -rw-r--r--. 1 tbalius bks 24660016 Jun 17 12:27 vdw.vdw
 
   -rw-r--r--. 1 tbalius bks 24660016 Jun 17 12:27 vdw.vdw
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 +
== Modifying INDOCK File ==
 +
 +
The following parameter how much orienting to do:
 +
 +
  match_goal                    5000
 +
 +
Reduce 1000 if docking takes to long.
 +
 +
The following parameter specifies the number of poses to write out:
 +
 +
  number_save                  1
 +
  number_write                  1
 +
 +
Consider writing out 100
 +
 +
Here are the minimization parameters:
 +
#                    MINIMIZATION
 +
minimize                      no
 +
sim_itmax                    500
 +
sim_trnstep                  0.2
 +
sim_rotstep                  5.0
 +
sim_need_to_restart          1.0
 +
sim_cnvrge                    0.1
 +
min_cut                      1.0e15
 +
iseed                        777
 +
 +
When these parameters are turned on, dock will minimize the 6 degrees of freedom (3 rotation, 3 translation) for the poses written out.
 +
All molecules written out will be minimized.

Revision as of 15:04, 28 June 2017

Scenario 1:

Use docking to predicted how Erlotinib (an approved drug) binds to the Epidermal Growth Factor Receptor

Search for Your Molecule in ZINC, Get Files for Docking from ZINC

Get the link from the zinc webpage and us wget to download:

wget http://files.docking.org/protomers/16/89/55/209168955.db2.gz

Put the path of the downloaded database into the split database index file (this file usually contain many db2 file):

ls /path/tutorial_for_webinar/dock3.7/209168955.db2.gz > ligands.sdi

Get the receptor structure from the PDB website

wget https://files.rcsb.org/download/1M17.pdb --no-check-certificate
Break Xtal into Receptor and Ligand Files

You may use a program like Chimera for this

Receptor file must be called: rec.pdb

Ligand file: xtal-lig.pdb


What if the crystal does not have a ligand:

Place atoms in the site were you want to dock. One way is to run sphgen and selecting spheres near residues in the site convert to pdb

Make the recptor file (remove alternative side chains):

grep "^ATOM" 1M17.pdb | grep -v ^................B > rec.pdb

Make ligand file:

grep AQ4 1M17.pdb | sed -e 's/HETATM/ATOM  /g' > xtal-lig.pdb

Run blastermaster: input rec.pdb, xtal-lig.pdb and makes all receptor file need for docking.

python $DOCKBASE/proteins/blastermaster/blastermaster.py --addhOptions=" -HIS -FLIPs "  -v

This command may take several minutes to run.

Here are the files that are produce:

 -rw-r--r--. 1 tbalius bks 3163 Jun 17 12:27 INDOCK
 
 dockfiles/:
 total 30388
 -rw-r--r--. 1 tbalius bks  1206051 Jun 17 12:27 ligand.desolv.heavy
 -rw-r--r--. 1 tbalius bks  1206051 Jun 17 12:27 ligand.desolv.hydrogen
 -rw-r--r--. 1 tbalius bks     3376 Jun 17 12:27 matching_spheres.sph
 -rw-r--r--. 1 tbalius bks   908086 Jun 17 12:27 trim.electrostatics.phi
 -rw-r--r--. 1 tbalius bks  3121095 Jun 17 12:27 vdw.bmp
 -rw-r--r--. 1 tbalius bks     1653 Jun 17 12:27 vdw.parms.amb.mindock
 -rw-r--r--. 1 tbalius bks 24660016 Jun 17 12:27 vdw.vdw

Modifying INDOCK File

The following parameter how much orienting to do:

 match_goal                    5000

Reduce 1000 if docking takes to long.

The following parameter specifies the number of poses to write out:

 number_save                   1
 number_write                  1

Consider writing out 100

Here are the minimization parameters:

  1. MINIMIZATION

minimize no sim_itmax 500 sim_trnstep 0.2 sim_rotstep 5.0 sim_need_to_restart 1.0 sim_cnvrge 0.1 min_cut 1.0e15 iseed 777

When these parameters are turned on, dock will minimize the 6 degrees of freedom (3 rotation, 3 translation) for the poses written out. All molecules written out will be minimized.