Protonation state change issue

choderalab / perses

Experiments with expanded ensembles to explore chemical space

http://perses.readthedocs.io

MIT License

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Protonation state change issue #375

Open pgrinaway opened 7 years ago

pgrinaway commented 7 years ago

Right now, the SmallMoleculeProposalEngine does not correctly respect protonation states, due to code that converts the OpenMM topology to an oemol (will raise issue there).

pgrinaway commented 7 years ago

This issue has been addressed for the nonequilibrium switching project by subclassing SmallMoleculeSetProposalEngine and skipping the round-trip through a SMILES string. I'm leaving this issue open, however, since it still needs to be resolved for the general case.

jchodera commented 7 years ago

(will raise issue there).

Could you clarify which codebase has the primary issue?

jchodera commented 7 years ago

The long-term fix for OpenMM Topology to OEMol conversion is to migrate to using the OpenMM-OEChem topology conversion functions in https://github.com/oess/oeommtools

This is being moved to a generally-available conda package that we will be able to use in the longer term, but it would be useful to see if we can temporarily borrow the code in the meantime (license permitting): https://github.com/oess/oeommtools/issues/7

jchodera commented 6 years ago

In #426 I was able to switch to a scheme where we always use canonical isomeric SMILES strings with explicit hydrogens so that we can be explicit in which protonation/tautomer states to consider for relative free energy calculations.

Let's keep this issue open, since we need to eventually support two modes of operation:

Specifying chemical species, with protomer/tautomer states drawn using their relative free energies in a second proposal step
Specifying exact protomer/tautomer species to use

jchodera commented 6 years ago

Changed label to enhancement since the bug has been addressed in #426