The correct respective ratios for these systems were 1:1 and 1:2, and these were a bonus challenge in SAMPL6. Binding free energies were predicted to be too favorable for guests 2 and 3 (Palonosetron and Quinine) which was presumed to be due to (a) AMOEBA parameters for the host resulting in single and/or double indentation of the macrocycle and (b) conformers of flexible guests locked during solvation in water vs binding in solvated complex . In subsequent studies, revised AMOEBA results reported the improved ME and RMSE to 1.20 and 1.68 kcal/mol respectively, though this was after challenge results were released.