2024-02-23 Cavender/Friedman

Fitting strategies

• QM parameter fits

  • Fitting pairwise energy differences

    • MGilson wants to prioritize this

  • Generating new QC training data

    • OpenFF QCArchive repo here:

    • Peptides longer than capped 3-mers

      • Cluster 4-mers from PDB database

      • Goal is to find structures that sample long-range interactions (e.g. H bonds) not present in 3-mers

      • Cap cluster centroids and compute single point energies

      • Anika is going to start here

    • Capped 1-mers with implicit solvent

      • Likely requires generating small molecule QC data with implicit solvent as well

      • Beyond the scope of making a baseline protein FF

• NMR observable fits

  • BICEPS from Voelz group for fitting to J couplings

    • Technical challenges to install new software and scale up to bigger fitting problems

  • Fit Lennard-Jones parameters to helicity

    • Straightforward to adapt existing scripts to do this

    • Need decision about what LJ parameters to change

    • Need experiments to test whether this breaks other interactions, e.g. with drug-like small molecules

Overview of Chapin’s fitting workflow

• This repo has the fitting scripts for the v0.0.2 proteins force fields.

• Chapin will update scripts to v0.0.3 and add documentation

• Post-Sage-2.1 OpenFF workflow is based on this repo: