Prepare a query model
After we have generated our reference structure (Prepare a reference structure) we can now proceed with building structures for which we do not have an x-ray structure. We will set up ligand with id M77 in this tutorial.
Process ligand file
We will use Antechamber to build ligand parameters:
antechamber -i M77_H.pdb -fi pdb -o prepi -fo prepi -c bcc -s 2 -nc 0
parmchk -i prepi -f prepi -o frcmod
Glide docking
With Glide we will use the prepwizard to generate the maestro files (.mae) needed for the docking. We will dock to the receptor structure generated in step Prepare a reference structure.
Prepare the receptor structures:
# Prepare receptor for Glide docking
reduce -Trim receptor.min.amb.pdb > receptor.pdb
prepwizard -WAIT receptor.pdb receptor.mae
# Prepare ligand for Glide docking
reduce -Trim M77_H.pdb > M77.noH.pdb
prepwizard -WAIT M77.noH.pdb ligand.mae
cat<<EOF>glide_grid.in
USECOMPMAE YES
INNERBOX 10, 10, 10
ACTXRANGE 30.000000
ACTYRANGE 30.000000
ACTZRANGE 30.000000
GRID_CENTER 6.989, 10.156, 2.855
OUTERBOX 30.000000, 30.000000, 30.000000
ENTRYTITLE receptor
RECEP_FILE receptor.mae
GRIDFILE glide-grid.zip
EOF
cat<<EOF>glide_dock.in
USECOMPMAE YES
RINGCONFCUT 2.500000
POSES_PER_LIG 1
GRIDFILE glide-grid.zip
LIGANDFILE ligand.mae
EOF
# Make the grid
glide -WAIT glide_grid.in
# Run docking
glide -WAIT glide_dock.in
# Convert to PDB files
pdbconvert -imae glide_dock_pv.maegz -opdb glide_dock.pdb
# Remove hydrogens
reduce -Trim glide_dock-2.pdb > ligand.glide.noH.pdb
grep "HETATM" ligand.glide.noH.pdb > tmp
mv tmp ligand.glide.noH.pdb
This step should provide you with following file(s):
- ligand.glide.noH.pdb
- One docking mode for the query ligand
Amber
Amber paramter/topolgy, and coordinate files can be generated with the following Leap script:
cat<<EOF> build
source leaprc.ff10
source leaprc.gaff
loadAmberPrep prepi
loadamberparams frcmod
set default PBradii mbondi2
receptor = loadpdb receptor.pdb
ligand = loadpdb ligand.glide.noH.pdb
saveamberparm receptor receptor.prmtop receptor.inpcrd
saveamberparm ligand ligand.prmtop ligand.inpcrd
complex = combine { receptor ligand }
saveamberparm complex complex.prmtop complex.inpcrd
EOF
tleap -f build
This step should provide you with following file(s):
- receptor.prmtop receptor.inpcrd
- Amber topology and coordinate files of the receptor.
- complex.prmtop complex.inpcrd
- Amber topology and coordinate files of the receptor-ligand complex.
- ligand.prmtop ligand.inpcrd
- Amber topology and coordinate files of the ligand.
Convert back to PDB files
# Convert to PDB-files
ambpdb -p complex.prmtop < complex.inpcrd > complex.amber.pdb
ambpdb -p receptor.prmtop < receptor.inpcrd > receptor.amber.pdb
# Convert to SYBYL mol2-files
top2mol2 -p receptor.prmtop -c receptor.inpcrd -o receptor.sybyl.mol2
top2mol2 -p ligand.prmtop -c ligand.inpcrd -o ligand.sybyl.mol2
# Fetch the ligand, and save to a seperate PDB file
grep "M77" complex.amber.pdb > ligand.amber.pdb
These files should now be sufficient to carry out a docking experiment (Protein-ligand docking).