We find that AHFE calculation repeats for lig 23475, which has a maximal partial charge di erence of 0.01 e, converge to values within 0.5 ± 0.2 kcal/mol (Figure ). In contrast, repeats of lig ejm 43, which has a maximal partial charge di erence of 0.06e, converge to a much larger range of 3.81 kcal/mol.