Prepare a receptor with a cofactor for docking

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This page is written by Trent E. Balius (FNLCR) on March 28, 2020.

This is for cases where the cofactor does not already have cofactors.

For the receptor, I use Chimera's DOCKprep module to remove solvent, add in missing atoms for residues, and remove alternative side-chains.

I run the blastermaster on the structure without the co factor to protonate the protein with reduce.

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

I visualize the protonated receptor and make sure that it seems correct.

I prepare the co-factor in chimera adding the hydrogen to the structure. I then run antechamber on that protonated mol2 file using this csh script:

cat ../GTP_charge/002.cofprep.antechamber.csh

 #! /bin/tcsh
 
 # setenv AMBERHOME /nfs/soft/amber/amber14
 
 set mountdir = `pwd`
 set filedir = ${mountdir}/../
 
 set workdir = ${mountdir}/cof
 
 rm -rf $workdir; mkdir -p $workdir; cd $workdir
 
 set charge = -4  # <--- you need to changes
 
 cp $filedir/Q61L_GTP.pdb cof.pdb # <--- you need to changes
 #cp $workdir/33443.pdb lig.pdb
 #sed -i 's/<0> /LIG/g' lig1.mol2
 
 $AMBERHOME/bin/antechamber -i cof.pdb -fi pdb -o cof.ante.mol2 -fo mol2
 $AMBERHOME/bin/antechamber -i cof.ante.mol2 -fi mol2 -o cof.ante.charge.mol2 -fo mol2 -c bcc -at sybyl -nc ${charge} 
 $AMBERHOME/bin/antechamber -i cof.ante.mol2 -fi mol2  -o cof.ante.pdb  -fo pdb
 $AMBERHOME/bin/antechamber -i cof.ante.charge.mol2 -fi mol2  -o cof.ante.charge.prep -fo prepi
 $AMBERHOME/bin/parmchk2 -i cof.ante.charge.prep -f  prepi -o cof.ante.charge.frcmod

Add the co-factor to the dock parameter files.

Copy the default parameter files from DOCKBASE:

 cp $DOCKBASE/proteins/defaults/prot.table.ambcrg.ambH  $DOCKBASE/proteins/defaults/amb.crg.oxt . 

Here are a python library and a python script that I use to to prepare the files to create amb.crg.oxt and prot.table.ambcrg.ambH for the cofactor

 https://github.com/tbalius/teb_scripts_programs/blob/master/zzz.scripts/mol2.py
 https://github.com/tbalius/teb_scripts_programs/blob/master/zzz.scripts/mol2toDOCK37type.py

Here is how to run the script:

 python ${TEB_SCRIPTS_PATH}/zzz.scripts/mol2toDOCK37type.py ../GTP_charge/cof/cof.ante.charge.mol2 temp

Add the parameters generated from mol2toDOCK37type.py

 cat temp.prot.table.ambcrg.ambH >> prot.table.ambcrg.ambH
 cat temp.amb.crg.oxt >>  amb.crg.oxt
 Use a text editor like vim to check the file and remove white space. 
 rm working/ -rf; mkdir working; cp rec.crg.pdb working; $DOCKBASE/proteins/blastermaster/blastermaster.py --addNOhydrogensflag --chargeFile=`pwd`/amb.crg.oxt --vdwprottable=`pwd`/prot.table.ambcrg.ambH -v