2020-11-18 Bespoke Workflow Meeting notes

Results of different fitting strategies

• JH – Tried using (1) all torsion terms available, (2) just parsley torsion terms.

  • Best performance has been when doing just parsley torsions.

• JH – Is there any downside to only doing ONE bespoke parameter on top of Parsley? Like, if there were several torsions running through a central bond, could we bespoke-fit just one of them?

  • DM – Trying to think of cases where things on different sides of a central bond AREN’T as rigid as aromatic rings, and might need to know about their flexibility. We wouldn’t want to flex certain parts of end groups.

  • JH – I’m assuming that they’re relatively rigid

  • SB – Could we make SMARTS where it’s the entire molecule SMILES, with the 2- and 3- atoms tagged explicitly, and any atom that is in the 1- or 4- positions would be written as a wildcard.

  • DM – Not sure that this would work, this might break something in the construction of SMARTS.

• JH – Found some cases where we do poorly relative to GAFF. Refitting
  (?starting from GAFF?) could fix these. Where would be the best place to report these?

  • DM – Striketeam channel. Trevor could use this info.

  • JH – I use a higher energy limit before downweighting, might be important to mention as well. Will also try running with different priors.

• JW – If fitting multiple torsions would produce a certain energy profile, are we sure that a single torsion would reproduce the same energy profile? Or would it be necessary to include many to encode different phases?

  • (General) – This isn’t mathematically proven, but it seems likely based on our experiments that fitting a single torsion is “good enough”

  • DC – Case like dibromoethane would trigger this sort of behavior.

  • JH – Right, I had to split that into multiple terms.

• DM – If we come up with code to generate a single torsion SMIRKS that “fits everything” for a particular rotatable bond, we should share that with JM.

• DM – The question of SMIRKS construction overlaps with WBO fitting. Want to fit torsion parameters to get barrier height.

  • JW – Would it be simpler to look directly at QM - MM energy (where the MM torsions of interest are zeroed)?

  • DM – That’s another option, but we already have the tooling to do the original idea using ForceBalance, so let’s pursue that first.

Vsties in GeomeTRIC

• CR – LPW accepted the PR into GeomeTRIC for doing vsites. May need to do another PR into torsiondrive as we test more.

Doing xtb torsion scans

• JM – Looking to do optimizations/torsions scans using XTB

• JH – Shows notebook, additionally would require conda install xtb-python – Warning – XTB only works on Linux

• JH –