Anchored Docking

This tutorial describes docking while anchoring specific ligand atoms to target coordinates in space. The ligand atoms can be specified using SMARTS patterns as described in step 2. The defined ligand atoms will be penalized by large energies if they deviate from the target coordinates. This works only with autodock_gpu.

Knowledge of the basic docking tutorial is assumed. Only the steps that differ from basic docking are written here.

1. Receptor preparation

Prepare receptor as for basic docking and make sure to use option -g to write the input file for autogrid (.gpf extension).

2. Ligand preparation

With mk_prepare_ligand.py Use option –add_atom_types to type phenol oxygens that are ortho to a carbonyl with atom type OX. The SMARTS “[#1][O]ccC=O” matches such phenol oxygens. In this SMARTS, the second atom is the one we want to type, hence we use “IDX”: [2].

mk_prepare_ligand.py --add_atom_types '{"smarts": "[#1][O]ccC=O", "IDX": [2], "atype": "OX"}' -i ligand.sdf -o ligand.pdbqt

If more than one atom are subjected to the anchoring potential, it will likely be impossible to fit more than a single atom near the target coordinates. Since the docking scores will force all matching atoms to be as close as possible to the target coordinates, unreasonable binding modes are likely. In ligand.sdf there are two phenol oxygens, but only one is ortho to a carbonyl, so the provided SMARTS matches only one atom. The number of matched atoms can be verified in the ligand PDBQT file written in step 3.

3. Run autogrid

The .gpf file was written by mk_prepare_receptor.py with -g option. Here’s an example call to autogrid:

autogrid4 -p rec.gpf -l rec.glg

4. Create a new map with a penalty

The penalty is a high score (kcal/mol) everywhere except near the target coordinates. By default, a 1.2 A radius is used for the un-penalized volume.

python addbias.py -i rec.OA.map -o rec.OX.map -x -3 11 25.2

5. Add OX map to FLD file

python insert_type_in_fld.py rec.maps.fld --newtype OX

9. Dock

autodock_gpu -L ligand.pdbqt -M rec.maps.fld -T OX=OA
mk_export.py ligand.dlg -o ligand_docked.sdf