During the total ∼2'000'000 minimizations for set P, we realized that the approach yielded unreasonably small energies for two conformers of compound P9 (e.g., the free energy is more than 100 kJ mol -1 smaller than the median of the ensemble). In order to exclude conformations that had such high deviations in a systematic way, all conformations with free energies more than four standard deviations away from the ensemble median were excluded. Further, for compound P10, which is an atropisomer, only conformers of the correct isomer were considered for the comparison to the explicit-solvent reference simulation.