JM – We’ve been working on fitting torsion terms, based on SMIRKS proposed by CBy.
PB – Looking at WBO vs. barrier heights
CBy – TIG3 barrier separation may be due to SHORT conjugated alkenes, where some bond remain more double-ish and single-ish.
CBy – Reminds me of tetraphenylbenzene, where naive ffs kept barrier pretty low
DM – Yes, but important to recall that we’re splitting out ring bonds.
CBy – Largely concerned by the scale – The lower WBO cluster for TIG3 ranges from barrier heights of 5 to 80 kJ/mol, and we’ll assign all of them a barrier height of 25
CBy – TIG7: The WBO range is super narrow in these datasets. Maybe there really isn’t WBO-dependence in these sets/for this torsion.
CBy – I'm thinkng that we do want a WBO dependence for TIG7.
CBy – From the Rowley data I’ve seen, TIG7 should be one of the really valuable central bonds.
CBy – Two big principles
THe ones jessica is working on/the relationship with other valence terms
When we see a cluster of points like in the TIG7 plot, it means they’re not very dependent on WBO, and the parameter may need to be separated out
TIG8
CBy – This is a 5-membered aromatic ring connected to a pyrrole.
CBy – Looks like we don’t have enough data.
Additional datasets?
JW – Protein fragment datasets may be good
DM – There will be a ton of redundancy there, right?
JW – Yes, so maybe it’s not a very good set
CBy – A dataset that we’re going to use should pass some conditions:
It should have a decent range of WBO values for the bond of interest (>0.2)
Should have a torsion barrier range that’s worth looking at.
All involved training sets should show the same variation (the range shouldn’t be due to systematic difference between datasets)
Is one dataset’s X and Y range strictly inside of another’s?
DM – Should split this into two problems:
Which SMARTS should we use?
Which QM dataset should we use for fitting it?
Basically make sure we ingest a lot, but avoid Lim benchmark molecules
CBy – Agree. On TIG6 plot, I’m optimistic about the green/”Substituted phenyl” set. Those don’t have many substituents at the atoms adjacent to bridgeheads.
(General) – These “barrier heights” are the relative QM energies – No correction has been made for MM energy components!
LPW – We’ve often discussed subtracting certain MM energy terms from QM energy profile to try and distill out contribution from other terms.
JM – My plans
JM – Calculate out other energy components, and do single-molecule fits
DM – If we use FB to fit, then the torsion barrier height is implicitly done including the other MM energy components. Then we could plot the barrier height from the MM energy profile.
LPW – That sounds like a reasonable approach.
LPW – One idea that I had is: We could fragment an individual molecule for which we’re trying to calculate a torsion barrier (every point in the torsion drive), then cleave the molecule and calculate their noncovalent energy.
DM – How would we deal with dangling bond? There wouldn’t be room for capping groups.
LPW – Agree that we’d need to cap, but not sure how.
JW – Use SAFT/SAPT?
LPW – Agree that that would work. That would do 3 calcs – fragment 1, fragment 2, and both together. Then it tries to decompose energy into components, but which may not be meaningful.
DM – Agree that LPW’s approach would be valuable, though I’m not sure how to implement
CBy – Agree. Would like to think more about decomposition idea. Very concerned about error in energies due to sterics. Maybe a first pass would just remove high-steric-energy mols. Could use MM energies to determine that.
HJ – Wanted to ask about fitting plan. If you fit parameters to torsion profile, there are a ton of knobs to set (eg, can other bonded terms change?).
DM – We only wanted to fit one torsion in each case.
DM – Plans for moving forward:
Energy decomposition idea is good but won’t be ready on sage timeline.
Do MM calcs and filter out molecules with high-magnitude vdW or Electrostatic energies.
Add Comment