Particularly, performance in prior SAMPL challenges was highly variable by method and target, and no clear method emerged as reliable across all systems or most systems. Both SAMPL3 and SAMPL4 included some guests in cucurbituril family , with the best RMS errors typically being around 2.5 kcal/mol unless empirical corrections were included , and no method stood out across both challenges . SAMPL4 also included cavitands. In SAMPL5, the best RMS error was closer to 3 kcal/mol , but correlation with experiment for this approach was not good. Methods based on explicit solvent and electronic structure calculations were noted to appear relatively consistent and generally provide the greatest reliability across all SAMPL challenges , but also had considerable room for improvement. In general, predictions for cavitands seemed to be modestly more accurate whereas clip-based hosts have been more challenging in prior challenges (like CB-Clip in SAMPL5 ). Thus, in the present challenge, we hoped to learn whether we might see a method or methods with significantly improved accuracy relative to prior challenges, and whether one might emerge that performs reasonably well (e.g. RMS error under 3 kcal/mol) across multiple host classes, as this has not typically been the case in prior challenges.