The optimized radii also showed encouraging transferability from host-guest systems to 59 protein-ligand systems. However, the new radii are significantly smaller than the baseline radii and lead to excessively favorable hydration free energies (HFE). Thus, users of the OBC2 GB model currently may choose between GB cavity radii that yield more accurate binding affinities or GB cavity radii that yield more accurate HFEs. We suspect that achieving good accuracy on both will require more far-reaching adjustments to the GB model. We note that binding free energy calculations using the OBC2 model in OpenMM gain about a 10x speedup relative to corresponding explicit solvent calculations, suggesting a future role for implicit solvent absolute binding free energy (ABFE) calculations in virtual compound screening. This study proves the principle of using host-guest systems to train potential functions that are transferrable to proteinligand systems, and provides an infrastructure that enables a range of applications.