To address these issues, the Ponder group used a separate set of free energy calculations to compute the binding free energy to each host conformation (indented and overlapping). However, the resulting free energies are sensitive to the choice of host conformation, since it does not relax back on simulation timescales, so they needed to estimate the relative free energy of the two unligated host conformations. In their submissions, their ranked AMOEBA/DDM/BAR submission assumes the indented TrimerTrip conformer is 2.84 kcal/mol more stable than the overlapping conformer, while the AMOEBA/DDM/BAR/ALT1 method assumes the overlapping conformer is 2.41 kcal/mol more stable than the indented, and the AMOEBA/DDM/BAR/ALT2 assumes both conformers are equal in free energy. The non-ranked AMOEBA submissions performed better than their ranked counterpart by almost all of the error metrics (Table ). Most of the improvement was attributed to better agreement for clip-g6, clip-g7, clip-g8, clip-g9, and clip-g11 when using an overlapping conformer. The Ponder group suggests that these results indicate that larger and bulkier guests prefer the overlap/spiral conformer(s), while the smaller guests prefer the indented conformer .