In-house reference calculations varied only in the energy model chosen while all other simulation parameters remained constant. As seen in Table , the performance of a reference method with a particular energy model varied across host. For example, we see greater predictive accuracy for WP6 systems when using OpenFF 1.2.0 followed by the newer OpenFF 2.0.0, opposed to GAFF2.11. Another group used an EE approach with OpenFF 2.0.0, and submitted additional predictions with variations of the method ( method names with EE in Table ), granting opportunity to cross compare EE methods with reference method (APR/OFF2.0.0/TI3P/MD-US/MBAR) for the WP6 dataset. Briefly, differences in the EE methods were in the application of Wang-Landau (WL) condition thresholds (0.02 for host-guest complex and 0.01 for guest), whether all data was used in weighted averages to include contributions of host and guest microstates to BFEs, or if all host microstates are considered, or when only the WP6 host with a formal charge of -8 is considered. For more details on these methods, readers are directed to main/host_guest/Analysis/Submissions/WP6/ and .