Our default force field, OpenFF “Sage,” works well on a wide variety of organic molecules relevant to drug design. However, projects involving more exotic functional groups may be limited by low force field accuracy. To address these challenging cases, the Open Force Field Intitiative provides a tool, “BespokeFit,” for generating custom parameters for the specific chemistry of a target molecule. These custom (or “bespoke”) parameters can now be used in RBFE calculations in OpenFE.
See the BespokeFit cookbook for instructions, and the February 2025 update slides (starting on slide 20) for more information.