Parameter type MMFF OPLS3 OPLS3e Sage (OpenFF 2.0.0) Bond Such an approach to transferable FF design is often successful as evidenced by numerous retrospective and prospective studies, which show good agreement between experiment and simulation. Critical applications of FFs include alchemical free energy calculations, which have become a widespread, relatively low-cost computational tool to aid the identification and development of high binding affinity small molecules in the early stages of drug discovery campaigns . However, due to the vast size of chemical space, and the local limitation of atom types used to describe these environments, the number of parameters required for broad, accurate coverage has tended to increase dramatically during FF development. For example, the most recent OPLS3e FF library contains ∼150 K torsional parameters (Table ) . has replaced atom-typed parameter encodings with a technique termed direct chemical perception .