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Aspirational API notebook demo | JC – PDB has been deprecated, so make sure that anything we can do with PDB can be done with MMCIF or other supported formats JC – PDB substructures have some standard connectivity defined. In the chemical component dictionary. IP – Will use pattern matching using something like SMARTS JC – When loading the PDB, remember that you can’t do SMARTS matching. So you either need to do a more limited “template” matching. So use either chemical component dictionary, or another officially-specced source from RCSB.
JC – If we load from a “common components dictionary”, then we don’t need to specify percieve_residues(nucleotides=True) JC – Treat hierarchy perception with a factory convention. Maybe consistent residue “flavors” that are accepted by lots of different API points. JC – There’s some python convention where you don’t have to treat metadata as a dict, and can instead just operate on direct attributes of molecule.metadata MH – Are you literally using MDTraj for the selection? JC – Is the residue-attachment a realistic use case? I’m not sure that it is, and I’d use SMIRKS for this.
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How to do chemical transformation? | JC – This is more complicated than what we do. We load the beginning and end point as separate SDFs, and then run a MCSS to get the mapping. So we don’t need in-house support for these sorts of modification. DR – Are we sure? What if I’m transferring from one unnatural AA to another?(not in the chemical component database)? JC – So, if we have a representation of a molecule before attaching to an amino acid… This seems unlikely. JC – Why not use SMIRKS? DR – Would a single MCSS match provide all the info we need to call this method? JC – Most common operation we need to do…
JC – hybrid_molecule seems to have the info we want, but we’d expect it from a much better API. So you’ll need to commit to exposing a much bigger API for this to be useful JC – The thing I really want is “take this alanine and mutate it into glutamine”, and handle the MCSS and everything yourself. Two strategies for residue replacement Use case for Perses 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). DR – We don’t have to supply hybrid topology. Return atom index mapping. OE doesn’t have this functionality. DR – OpenMM topology – don’t know what happens with that – ended up using mdtraj tops. DR Said he could try to comment Perses' code to point out where they want drop-in replacements for OpenFF topology object.
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Feedback we want form them | Feedback on the return type for the substructures. rdkmol OEmol etc? Reaction information in general. What reaction information format(s) to expect. No high level API for the hybrid topology from our part.
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