TYK2 torsion refits | /wiki/spaces/~102144901/pages/786628747 JH – Sometimes the same torsion is assigned multiple times around the same bond. Two problems: (1) ForceBalance ends up only changing one of the Chemper-defined torsions (2) optimization takes a LONG time DM – May be JA – This particular case deals with aromatic rings, where the torsion angles are strongly correlated. In something like cyclohexane there could be more of a case for keeping the parameters separate. DM – Could just fit one torsion about each rotatable bond
JH – Tried improving computational speed by reducing the number of parameters I’m optimizing. Calculated quality vs. performance for various simplifications (like just using Parsley types) (General) – The computational cost is much lower if we don’t reoptimize the geometry. But it’s important that we refit the geometry. JA – Would there be a way to prune parameters to reduce the search space? JH – Using Parsley as a guide has helped with this. And I do agree that it would be helpful to prune early on DM – This may be premature optimization JW – Is it always the case that the important k values will be visible early on? Or do we risk pruning important terms early on? JA – It would probably still be safe
HX – What we do to validate the set, in addition to the torsion scan, we also generate local minima, and ensure that we minimize to those. JW – So, is the big limiting step the speed of MM minimization? JH – Would be interested in an intermediate benchmark before full FEP calculations DM – Agree that testing against optimized geometries is a good idea here. JH – So, is the idea to generate random confs that aren’t in the torsion drive? DM – I think that would work. HX – That’s one of our validation steps. We also look at Hvap and other physical properties. But internal energies are the most concrete thing to test against. DM – If we don’t want to generate new QM data, would the optimization trajectories be a good source of confs+energies? HX – Yes JH – a bit concerned about this, since those structures will also have identical torsion angle values DM – Could also do single point calcs on random/omega geometries. JH – Should I do this on the fragments or the whole molecule? DM – Both? JH – Sure
There’s one case where the fragment fit gets WORSE, but the whole molecule fit gets BETTER. DR +JH – How will we feed the new files into openmmforcefields? (General) – We’ll make a new FF for each molecule, which is a concatenation of Parsley and the bespoke terms for one molecule. JW will provide JH and DR a code snippet for adding the current directory to the FF-loading entrypoint
- Jeffrey Wagner will provide a code snippet to Josh Horton and Dominic Rufa to show how to load a FF from the current directory in openmmforcefields
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