Prepare a receptor with a cofactor for docking
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