ADL: AutoDockFR: how to prepare ligands for covalent docking?

Michel Sanner sanner at scripps.edu
Sat Oct 10 10:11:57 PDT 2020


Hello

From: Gao Zhenting <zhentgpicasa at gmail.com>
Date: Saturday, October 10, 2020 at 7:02 AM
To: Michel Sanner <sanner at scripps.edu>, "autodock at scripps.edu" <autodock at scripps.edu>
Subject: AutoDockFR: how to prepare ligands for covalent docking?

Dear Sanner,

I am learning covalent docking workflow of AutoDockFR. And I finished the the tutorial.
The ligand is provided for the tutorial, but there seems no document about how to prepare the ligand.

I noticed that 4 atoms from sidechain of cysteine is included in the ligand pdbqt file, and they are put at the head of the pdbqt file, with atom index ranging from 1~4. If I regenerate the ligand file by prepare_ligand4.py, then the 4 atoms will be move at the end of the pdbqt file with index ranging from 23~26. With the regenerated ligand pdbqt file, the covalent docking pose is wrong, with a positive docking score.

Yes, this is correct. The ROOT / ENDROOT block of atoms has to contain the atoms forming the covalent bond and be the root of the torsion tree because these atoms should not move as the conformation of the ligand is modified during docking.’
If you run prepare_ligand4.py you need to specify which atom to use as a root for the torsion tree. If nothing is specified, prepare_ligand4.py will pick a central atom. The root atom can be specified using -R on the prepare_ligand4.py command line. I recommend running prepare_ligand4.py a first time on the ligand, then look at the file and find the number of the atom you want to be the root and re-run prepare_ligand4.py with -R Num to change the torsion tree and make sure the atoms forming the covalent bond are at the root.

With the files you sent me, running

prepare_ligand4.py -l 3c9w_ligandWithSideChain_random_prepared_covalent_out.pdbqt -o ligandWithCorrectRoot.pdbqt -R 25

should create a ligand with the correct atoms in the root


-Michel

Could you help me on how to prepare the ligand file?

Best regards
Zhenting

Commands of my workflow:


~/tools/MGLTools-1.5.6/bin/python /home/zhentg/tools/MGLTools-1.5.6/MGLToolsPckgs/AutoDockTools/Utilities24/prepare_ligand4.py -l ../../data/3c9w_ligandWithSideChain_random.pdbqt -o 3c9w_ligandWithSideChain_random_prepared.pdbqt

~/tools/ADFRsuite-1.0/bin/adfr -l 3c9w_ligandWithSideChain_random_prepared.pdbqt -t 3c9w_cov_cmdline.trg --jobName covalent -C 1 2 3 --nbRuns 8 --maxEvals 100000 -O --seed 1

~/tools/ADFRsuite-1.0/bin/adfr -l 3c9w_ligandWithSideChain_random_prepared.pdbqt -t 3c9w_cov_cmdline.trg --jobName covalent -C 26 25 24 --nbRuns 8 --maxEvals 100000 -O --seed 1


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