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

Download M77 PDB 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).