We also learned important lessons about host binding modes in these systems. The use of multiple binding orientations, and/or microstates with the ATM approach had success in the SAMPL9 bCD dataset, and the method's previous success in SAMPL8 shows general applicability. The method thus has been among the most accurate across host categories. From the success of this method, we learned that multiple binding orientations in the primary and secondary face need to be considered (at least when binding mode(s) are unknown a priori) for most approaches, otherwise relevant configurations would not be sampled at simulation time scales leading to inaccurate BFEs. However, results with the GRO-MOS 53A6 GLYC ( DD/GROMOS-53A6_glyc/SPC/MD) force field had great agreement with the experimental binding free energy for PMT guest in complex with both bCD and HbCD, despite only considering one orientation, possibly due to this force field's more careful treatment of the hexopyranose based carbohydrates. These seemingly contradictory findings may indicate that systems with the PMT guest have a single and distinct dominant binding mode, whereas other cyclodextrin systems have a different binding mode and perhaps multiple equally dominant modes.