In this manuscript, we refer to calculations where the guest functional group in the bound state is at the primary face of cyclodextrin with a -p suffix, and calculations where it is at the secondary face of cyclodextrin with a -s suffix.. Thermodynamic integration and the multistate Bennett acceptance ratio estimator (MBAR) were used to compute the binding free energy (ΔG°). The results presented in the main text are those analyzed using thermodynamic integration to be consistent with prior analysis presented in Henriksen, et al. . The binding enthalpy (ΔH) was computed as the difference in mean potential energy of the bound state (in the absence of any restraints) and the unbound state (where the guest is held far away from the host, but the conformational restraints on the host are disabled). The binding entropy (ΔS°) was computed by subtraction using ΔG° and ΔH.