2021-04-22 Wagner/Pulido API planning meeting notes

Perses meeting notes review – Things to cover in API notebook

• Distilling discussion points from this morning’s Perses check in 2021-04-22 Perses meeting notes

• Residues → molecules, with and without capping

• Loading MMCIF or PDBx

• Incorporate CCD into our substructure library – Can one substructure library handle SDF → atom types AND PDB → bond orders

  • Let’s take a look at the structure of this, and decide whether we want to use it as our data format

• Double check that our flexible-hierarchy-handling plans look like a proper “factory” convention.

  • Offer easy-to-access common “flavor(s)” for hierarchy perception

• Treat metadata as dataclass instead of dictionary?

  • JW – I like the user-friendliness of this approach, but don’t know whether it will work well with pydantic. So let’s do the friendliest thing that pydantic allows.

• Chemical modification API?

  • Should we use SMIRKS or merge_molecules?

    • JW – I don’t know what the tradeoffs of these two approaches will be. Maybe we implement support for both in a private API, and see how they go?

    • Does pydantic allow _ to indicate private method names?

• Does hybrid_molecule have the API that Perses needs? Should the expanded API live in the Topology object?

  • JW – It doesn’t/won’t have the API that Perses needs, but it does have the information. So Perses can have a friendlier class that is intantiated by the information in this object, but anything that will provide a friendly API should live in Perses, so development of its features aren’t gated/blocked by OFF developer-time or release schedules.

Use cases

• Coming in with two separate complete SDFs and a mapping between them

  • Take one Topology, remove the old ligand, put in the new ligand and possibly an atom mapping. As a bonus, get back a hybrid molecule that maps the old and new ligand.

• Coming in with a protein, and switch to a different protomer/tautomer

  • Load a biopolymer, identify residues, ask OFFTop to mutate one residue into another, slice out the before- and after- residue, and use OEChem to do the MCSS so that Perses can control the atom mapping.

• Coming in with a protein, switch one residue to another from the chemical components dictionary

• Coming in with a protein, switch one residue to another NOT from the chemical component dictionary

• Cut a residue out of a protein, with or without caps. Possibly with caps informed by “undoing” the polymerization reaction (and allow reverse trips).

Other topics

• Molecule vs. Topology hierarchies

Notebook review