In total 8 of the 15 predicted free energies were within 0.65 kcal/mol of experiment while the predictions for Palonosetron and Quinine guests were in better agreement with experiments. The improvements were attributed to two factors: (a) the value of key torsion parameters for C(N)-C-amide N-carbonyl carbons of CB8 and CB7 were adjusted to improve the flexibility description of the host ring system and (b) a double annihilation scheme of electrostatics and van der Waals with annihilation of key guest torsions yielded much better conformational sampling and hence predictive accuracy. However, through the SAMPL6 challenge we had not yet seen methods using the AMOEBA force field dramatically outperform other methods prospectively.