the individual umbrellas can all be simulated in parallel, allowing for fast simulations, and expedited reference calculations with modest accuracy. (b) The APR method has been used in benchmarking studies, and default setting/parameters used in the method have been established for calculating thermodynamic measurements of host-guest systems similar to those present in SAMPL8 . (c) Given that the hosts and guests in this study are relatively rigid, the binding modes are well known, we thought the use of enhanced sampling may not be necessary in the majority of cases. At the same time, perhaps using this approach would also bring insight on where enhanced sampling provides the greatest benefits.