Overall for the TrimerTrip/clip-based systems, when we consider both ranked and non-ranked submissions, we believe the results suggest that any combination of the following may be limiting predictive accuracy: (a) chosen host conformer, (b) guest binding mode, (c) chosen energy model, and (d) water model. More specifically the general performance of the AMOEBA-based submissions pointed towards multipoles, polarization and/or shielding effects being important, especially as the guest becomes more hydrophobic, but the AMOEBA work (using multiple host conformers) also suggested host sampling could be an important issue since host conformers did not interconvert at nanosecond simulation timescales.