Protein/Ligand Preparation for Docking

@bowenliu16 raised a number of interesting questions about protein preparation on the gitter which don’t have great solutions within deepchem yet. I’m starting this thread to copy over the questions and discuss potential solutions:

1. What kind of protein preparation is done? Do we need to manually remove crystallized water and other ions? What about missing protein residues/loops?
   • dc.feat.hydrogenate_and_compute_partial charges is the current extent of protein cleanup. I don’t believe we handle water/ion removal. Also, no handling of missing protein residues/loops. https://github.com/pandegroup/pdbfixer by @peastman handles many of these issues, so the right answer might be to use PDBFixer to handle these issues.
2. How many ligands can be in the .sdf file to be docked at the same time?
   • I think we only support one-ligand per .sdf file right now. Should probably generalize to support multiple ligands.
3. And what time of ligand processing do we need to do? Eg is any 3D conformation fine? We also have to manually specify the protonation states and any tautomers right?
   • dc.feat.hydrogenate_and_compute_partial_charges is the only ligand processing right now. It partially handles protonation, but I’d wager it doesn’t do an excellent job. We don’t handle tautomers yets.

I’d love to hear suggestions on good ways to handle pdb-cleanup, protonation, and tautomers with existing open source tools 😃

CC @peastman, @joegomes, @evanfeinberg

[rbharath]

I’d recommend taking a look at some docking best practices guides. For example, perhaps this one: http://ablab.ucsd.edu/pdf/Rueda_Abagyan_Wiley_Chapter_123112.pdf

Making progress here basically requires us to implement these best practices guides in DeepChem.

[rbharath]

Closing this old issue. Let’s continue the discussion in https://github.com/deepchem/deepdock/issues/3