Overall, the UAFF RBFE and MD results suggest that both the improved partial charges on the zinc-coordinating residues, as well as the more restrained equilibration improve the ∆G predictions. However, improvements are still needed, especially in accounting for the change in the ligand charge in the presence of the metal. Similarly, the zinc coordination sites may be better conserved with a model that also modifies the zinc charge to account for polarization effects more accurately.