How to use Autodock just for (re)scoring
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Entering edit mode
7.3 years ago
se.raschka ▴ 140

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

docking scoring autodock • 7.2k views
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0
Entering edit mode
7.3 years ago
se.raschka ▴ 140

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?

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