2022-05-19 Protein FF meeting note

Nucleic acid support

Chapin Cavender

• Janssen RNA team working on modified antisense oligonucleotides reached out about OpenFF nucleic acid support

  • Chapin is meeting with the Janssen team on Monday, May 23

  • OpenFF is prioritizing support for proteins due to direction from governing and advisory boards

  • An OpenFF force field release supporting proteins will not happen before 2023

  • OpenFF is committed to supporting canonical nucleic acids, but the timeline for this is not clear

• Avenues for nucleic acid support

  • Parametrization of nucleic acids with Sage/Rosemary plus graph charges, which is unlikely to be competitive with contemporary RNA force fields like Amber OL3

  • Nucleic acid specific torsions for canonical nucleic acids

  • Bespoke torsions (or infrastructure to support fitting bespoke torsions) for covalent nucleic acid modifications

Protein QC datasets

Chapin Cavender

• Status of protein QC datasets

  • 2-D TorsionDrives on (phi, psi) for capped 1-mers

    • 25 / 26 complete

  • 2-D TorsionDrives on (chi1, chi2) for 23 capped 1-mers with backbone constrained to alpha helix or beta sheet

    • 44 / 46 complete

  • Three TorsionDrives (CYX backbone, GLU sidechain beta, LYS sidechain alpha) are failing on a small number of grid points (<1 %) due to geometry convergence. Should these still be used in parameter training?

• Additional QC datasets

  • Optimization dataset for 26 capped 1-mers

  • TorsionDrives on (phi, psi) for 52 capped 3-mers

    • 26 Ace-Ala-X-Ala-Nme

    • 26 Ace-Val-X-Val-Nme

  • Optimization dataset for 52 capped 3-mers