An issue that SAMPL host-guest challenge participants encountered in prior iterations was poor conformational sampling of the host (particularly with CB[n]-type acyclic receptors). Using WP6, which is macrocyclic but has some degrees of flexibility, can put focus on conformational sampling. The carboxylate arms of WP6 (OCH2CO2 groups) all can pass through the annulus (above or below the ring shape formed by the phenylene groups) to give a second host enantiomer . Thus, adequate sampling of these flexible regions may be necessary to achieve accurate predictions.