2022-07-28 Protein FF meeting note

Progress of LiveCoMS paper

MRS

• MRS – Just checking on status here

• CC – Blocker is on me - Replying to comments by reviewers but not done yet.

• MRS – Would be good to have this done before we put parameters out.

• CC – Internal plans are that we have all the information that we need, so we just need to get it into a coherent state for submission to a journal.

• MRS – Schedule?

• CC – Six weeks to submission?

  • MRS – So sept 12? That would work for me.

  • CC – Previous variability has been on waiting for external people to weigh in/provide info. I’ll have MG apply pressure and we’ll reach out to you if we need additional pressure.

crystal simulation validation thoughts?

MRS

Student in my group (who I think would be good) can be available to do it (at about 50% time)

• MRS – Student that was going to follow up for OM is not going to be continuing. There’s a new student who could work on crystal validation with David Case and Michael Wall. Availability would begin at the Fall semester (3 weeks from now). Is there enough information that we could come up with a discrete set of tasks for the new student to do?

  • CC – I think we have enough info from the LiveCOMS article to know which data we want to use. However we need to figure out what metrics to measure/determine how well simulations reproduce experiments

  • MRS – Could look into harmonics/reproducing electron densities. Could use the same techniques as Case and Wall for this?

  • CC – It seems like every paper on this topic performs the analysis a different way. So we’d want to run one or more xtal simulations of each system, and then run experiments on those systems to see if they reproduce experiments.

  • MRS – Who should I talk to about getting people/resources marshalled for this?

  • CC – Probably Mobley.

  • MRS – Could I check out the current state of the manuscript?

  • CC – Sure, I’ll send that over.

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Assessment of protein QC data

@Chapin Cavender

• CC will upload slides here

• Sets from slide 1:

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• CC – 3-mer torsiondrives that are in progress will only be used for validation, NOT training

• BS – Should check that the minimum energy structures in QM and MM are structurally similar.

  • CC – That should be nearly guaranteed, I’m keeping the heavy atoms involved in the torsion in the MM optimizations constrained.

  • JW – It may be good to harmonically restrain ALL the heavy atoms in the MM optimizations. Also we should keep in mind that the AM1BCC charges for these small capped molecules may differ from how the librarycharges look.

  • CC – Since this is an early experiment on single capped AAs (as opposed to larger, more realistic proteins), I’m not worrying about these yet.

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• Slide 13

  • JW – (Some wrong interpretation)

  • MS – It’d be interesting to see how ff14sb does on these (as opposed to sage)

    • CC – That’s a good idea, this could help us shape a baseline.

  • LW – On this plot, wouldn’t adding another MM force field add another bar about as tall as the MM energy bar (Sage)?

    • CC – Yeah, it wouldn’t make a lot of sense to talk about a single MM target if we have multiple MM force fields

• MS – How’s the timeline looking for this? I think we need a FF when we go in for grant renewal?

  • CC – My internal deadline is December

  • MS – That’s cutting it a bit close - We’ll want to file for renewal around Feb or March, and we’ll probably need to iterate a bit. So for next meeting, we should identify what the barriers are and how to remove bottlenecks.

  • CC – One place I could use additional person-hours would be software dev. I’d taken responsibility for the NMR data and then doing the analysis software next.

  • MS – It’d be good to look at a project plan with timing for tasks. I’ll be out of town in two weeks when we meet next.

  • CC and DN will coordinate a meeting to see how we can redistribute resources to meet a March FF deadline.

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