How to use Autodock just for (re)scoring

Question

[se.raschka]

I have some protein-ligand complexed that I have been docking with some other software and just want to use Autodock to evaluate those complexes. So, basically I just want to use it as a scoring function to take a look at the energy components - I don't want to re-dock the ligands into the protein binding sites.

From what I have found on the internet, I came up with this procedure, but I am not sure if this is the right approach, and also I get an error in the last step saying that "atoms are outside the grid".

autodock rescoring steps

1. Preparing the receptor

• need to add hydrogens if not present
• adds gasteiger charges to peptide

input:

• protein.pdb

output:

• protein.pdbqt

script:

prepare_receptor4.py -r protein.pdb [options]

---

2. Preparing the ligand

• add hydrogens if not present

input:

• ligand.pdb or ligand.mol2

output:

• ligand.pdbqt

script:

prepare_ligand4.py -l ligand.mol2 [options]

---

3. Generate grid parameter file

inputs:

• ligand.pdbqt
• protein.pdbqt

output:

• protein.gpf

script:

prepare_gpf4.py -l ligand.pdbqt -r protein.pdbqt [options]

---

4. AutoGrid: generate maps and grid data file

inputs:

• protein.pdbqt
• protein.gpf

outputs:

• protein.glg Grid Log File
• protein.*.map affinity maps for different atoms
• protein.maps.fld Grid data file
• protein.d.map desolvation map
• protein.e.map electrostatic map

command:

autogrid -p protein gpf

---

5. Generate docking parameter file

inputs:

• ligand.pdbqt
• protein.pdbqt

output:

• ligand_protein.dpf

script:

prepare_dpf4.py -l ligand.pdbqt -r protein.pdbqt [options]

---

6. Prepare .dpf file and run autodock for re-scoring

Remove seach parameters and append the "epdb" keyword, so that an examplary .dpf would look like this:

autodock_parameter_version 4.2 # used by autodock to validate parameter set
outlev 1                             # diagnostic output level
intelec                              # calculate internal electrostatics
ligand_types C HD N NA OA            # atoms types in ligand
fld rec.maps.fld                 # grid_data_file
map rec.C.map                    # atom-specific affinity map
map rec.HD.map                   # atom-specific affinity map
map rec.N.map                    # atom-specific affinity map
map rec.NA.map                   # atom-specific affinity map
map rec.OA.map                   # atom-specific affinity map
elecmap rec.e.map                # electrostatics map
desolvmap rec.d.map              # desolvation map
move lig.pdbqt                       # small molecule
about 17.6 22.2 32.6         # small molecule center
epdb                                   # small molecule to be evaluated

inputs:

• ligand_receptor.dpf

command:

autodock -p ligand_protein.dpf

Answer 1

[se.raschka]

Okay, I finally figured it out in 6 simple steps.

1. Preparing a protein
2. Preparing a ligand
3. Generating a grid parameter file
4. Generating maps and grid data files
5. Generating a docking parameter file
6. Running AutoDock

Answer 2

[se.raschka]

Okay, I managed to use AutoDock Vina for re-scoring, e.g.,

by creating a config file

receptor = protein.pdbqt
ligand = ligand.pdbqt
center_x = -2.491 # Center of Grid points X
center_y = 30.038 # Center of Grid points Y
center_z = -10.765 # Center of Grid points Z
size_x = 25 # Number of Grid points in X direction
size_y = 25 # Number of Grid points in Y Direction
size_z = 25 # Number of Grid points in Z Direction

and then run

vina --score_only --config config.txt --log your_filename.log

However, the output is not as detailed as the one that would be generated via AutoDock4.2

For example, what I get is:

Affinity: -2.06943 (kcal/mol)
Intermolecular contributions to the terms, before weighting:

gauss 1     : 51.97697
gauss 2     : 1133.84012
repulsion   : 7.41516
hydrophobic : 34.56441
Hydrogen    : 0.00000

(what is also weird is that the prepare_ligand4.py script to generate the .pdbqt file from the mol2 file removed the hydrogens)

In AutoDock4.2, the output would be, for example,

epdb: USER Estimated Free Energy of Binding = -6.54 kcal/mol [=(1)+(2)+(3)-(4)]
epdb: USER Estimated Inhibition Constant, Ki = 15.95 uM (micromolar) [Temperature = 298.15 K]
epdb: USER
epdb: USER (1) Final Intermolecular Energy = -7.14 kcal/mol
epdb: USER vdW + Hbond + desolv Energy = -6.33 kcal/mol
epdb: USER Electrostatic Energy = -0.81 kcal/mol
epdb: USER (2) Final Total Internal Energy = -0.20 kcal/mol
epdb: USER (3) Torsional Free Energy = +0.60 kcal/mol
epdb: USER (4) Unbound System's Energy [=(2)] = -0.20 kcal/mol

Anyone knows if this might be available through VINA somehow?

[saisai.sun]

Could you please tell me how to get the config file? I don't know how to get the x,y,z centre.Thanks a lot.