Challenge compounds to parameterize

[shuail]

Hi all,

We found the attached compounds are challenging for force field parameterization so we would like to share those data here to 1, see if Openff could parameterize it better. 2, potentially enlarge the chemical space of the dataset.

moles_WX.txt

Thanks! Shuai

Xtalpi Inc

[jchodera]

Hi @shuail! It would help to have some more information to help us follow up on this:

• Which specific OpenFF force field did you evaluate?
• What set of molecules did you evaluate?
• Did any of these molecules fail to parameterize, or did you simply note energetic discrepancies with quantum chemistry?
• What specific level of QM theory did you compare to? Was it the same as the level of theory used to parameterize Parsley?
• What testing methodology did you use to generate quantum chemical data and compare energies? Did you compare energies for the same geometries, or minimize independently with MM and QM from the same starting geometry?

Once we have these details, we should be able to look into this more deeply.

[davidlmobley]

I discussed this with Shuai. It turns out that these are molecules they have NOT tried Parsley on which seem to be not well treated by other force fields when compared to QM (torsion drives), especially GAFF and similar options. These are public library compounds selected by looking for cases where GAFF had poor performance. They are mostly from ChemBL.

It sounds like these would be good to prioritize for geometry optimization/torsion driving.