2024-05-02 Protein FF meeting note

Cap library charges

@Chapin Cavender

• MS: shows slight downside of LibraryCharges in that there should be charge bleeding from caps

• CC: AMBER RESP charges and CHARMM charges also enforce caps summing to zero – seems necessary unless caps always come in pairs

Fits with Amber charges

@Chapin Cavender

• JW: I was under the impression that ff14sb performed best with tip3p

  • CC: ff14sb tends to be insensitive to water model for folded structures. For unfolded ones ff14sb does perform best with tip3p. This also aligns with CSimmerling’s work

• Null 0.0.3 OPC does keep GB3 stabilized but does not fold 15-mer

• LS: I’m excited that Null 0.0.3 + OPC passes all tests except the 15-mer

• CC: Specific 0.0.3 folds 15-mer with all 4 water models on slide 18. But GB3 helix still destabilized

• CC: we had wanted a force field to pass both the 15-mer and GB3 benchmarks before starting the next step. Is that still the case?

  • MS: most single helices aren’t super stable – is a single alpha helical peptide too stringent a criterion?

  • CC: I think for this temperature (274 K), it’s roughly 50% helix and comparing the chemical shift not too stringent

• MS: previously mentioned using a different library of conformers …? (~34 min)

• CC: should we keep probing Null 0.0.3 + OPC

• AF: not a lot of man hours, can do a check after a couple microseconds

• DLM: if we can get a FF that works well with a 4 point water model vs spending more years on a 3 point one, I’d choose the first. We can hedge our bets here.

• Consensus: keep running other folded proteins while CC continues other pathways of investigation

• JW: do you have feelings about showing an in-progress protein FF at the annual meeting? We’re doing a tech demo and could feature it with warnings

  • CC: it depends. Not enthusiastic if it causes too much excitement

  • CC: a positive outcome is that it could demonstrate that we are closer to our goal from last year

  • DLM: we should put this in the annual report

  • JW: ok, won’t present live progress on protein FF