JW – IA, MT, and I will be working on infrastructure for having SMIRNOFF proteins in OpenFE calcs (maybe not public-facing, but some blessed infrastructure where we can submit these jobs for our internal benchmarking). We have two weeks of work planned on this for late July/early August |
Sage 2.3.0 updates PB – Slide 8 – What does ratio mean? PB (10) – 2.3.0rc1 is vdw and valence retrained? BS (17) – Chlorides and bromides are places where schrodinger would put a vsite CC (28) – Why not both equilibrate the slow ones for longer and loosen the restriction on …? DM (43) – If FF already disagrees with enthalpy of mixing, how would changing the experimental mixtures help? LW – My hypothesis is that the signal:noise ratio of having two points with different concs having the same exptl value is confounding the optimization. DM – Is expt usually spaced regularly? (yes) so maybe we could have the automation that selects the points pick the extrema LW – Yes, this would require a little work in evaluator but wouldn’t be too hard.
JC (50) – Given that you’re seeing a tradeoff where fitting an outlier pulls lots of other points out, do you think another parameter split would help relieve that? BS(52) – When you change FF a little bit, do you use some info from the last iteration or do you re-equilibrate every time? CC (52) – Understand constraints from compute, if that’s the limit then that makes sense. I am in favor of doing more thorough training on primary amines. LW – Yeah, would be in favor of bringing in some members of the validation set into the training set and using some of the slower-equilibrating amines. The added computational expense of the latter is probably worth it. CC – So not saving time … LW – Previous workflow … Now we do longer timescale sims for initial box equil and then save it for subsequent property calcs which can be quicker. CC – So new protocol is nto enough for the primary amines? LW – 10 or 20 ns was not enough time for the primary amines. But these are small enough that we could just let them run longer. One of my big concerns that changes in parameters would require more equil time (?)
PB – Equil time is a force field issue, or intrinsic to those molecules? LW – Good Q, I think it’s a starting condition issue. Packmol packs boxes loosely so it takes a long time for density to equilibrate, then enthalpy takes a while after that. But the lack of equil is more evident in densities. LW – Could equilibrate with a different FF. One other option is starting from previous iteration for the next iteration. But evaluator changes take a lot longer than I plan every time, so that’s a bottleneck with our resources. JW – Team cross training might help get more hands/eyes on evaluator performance issues
DM – (hydroxyl H something something) CC – GAFF has a 0 radius H, is that so much of a problem? DM – Yes, I showed that certain conditions with benzoic acid dimer can lead to atom overlap/energy explosion. This appears sometimes in simulation. There are some host-guest systems that you just can’t simulate with 0 radius hydroxyls. LW – We did see this going to zero in our fitting, and had to set it back. But if we can train the rest of the FF around this not being allowed to be 0 then we should be ok.
LW – Ok, so we’ll loosen restrictions on training set membership and pull some validation set mixtures into training. Regarding compute bottleneck - I’ll do benchmarks on vdW and valence fits, so we’ll know a bit about the amine problem. If those simple changes don’t work, then we’ll move on to bigger projects like … and co-training.
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