Our in-house reference calculations provided the only other non-ranked submissions for TrimerTrip. Our two sets of reference calculations (Docking/GAFF/YANK_REF and Docking/GAFF/YANK_REF_2) differed only in the choice of host conformer for clip-g11, where the latter submission used an alternate, relatively open host conformation to allow it to relax and adapt to the bulky cyclic guest in g11 (see Section 6.1.1), though this approach ended up not resulting in substantially different predicted binding free energies. Performance statistics for these reference calculations ended up being particularly poor in general Table . Error metrics for all (ranked and non-ranked) SAMPL7 methods for all host-guest systems. The root mean square error (RMSE), mean absolute error (MAE), signed mean error (ME), coefficient of correlation (R 2 ), slope (m), and Kendall's rank correlation coefficient (Tau) were computed via bootstrapping with replacement. Shown are results for individual host categories, as well as the artificially separated exoOA sub-dataset. Statistics do not include optional host-guest systems OA-g1, OA-g2, OA-g3 OA-g4, OA-g5, OA-g6, bCD-g1, and bCD-g2. Each method has an assigned unique submission ID (sid). Table (Tables and). The reference method gives free energies for all TrimerTrip host-guest complexes which are too unfavorable, similar to ranked MD/DOCKING/GAFF/xtb-GNF predictions. Both submissions used docking (VINA) to obtain guest poses without any MD (except that the MD/DOCKING/GAFF/xtb-GNF technique used SA-MD to obtain poses for four guests), GAFF parameters, the TIP3P water model, and AM1-BCC charges, so it may not be surprising that performance was similar. However, the MD/DOCKING/GAFF/xtb-GNF approach performed better for the case of the four guests where starting poses were established by SA-MD, with errors under 1 kcal/mol in those cases.