We also examined two different small-molecule force fields and observed similar performance. Particularly, we compared our two sets of reference calculations which differ only in the force field used (GAFF2 or OpenFF Parsley v1.2.0), and found that the force fields have similar performance (where on average predictions were within 0.5 kcal/mol of one another by comparing their predicted binding affinities). However, for certain systems (CB8-G5, CB8-G6, CB8-G7, TEMOA-G2, TEMOA-G4, TEETOA-G4, and TEETOA-G5) there is disagreement in the calculated values between GAFF2 and Parsley. The RMS difference between the two force fields were 3.00, 1.14, and 1.17 kcal/mol for CB8, TEMOA, and TEETOA, respectively.