There were systems where all methods systematically underestimated the truncation point (particularly MDM2-Nutlin and MDM2-Pip2). However, the best-performing methods generally showed an ensemble RMSE close to the optimal fixed truncation point minimum, and the N n 0 window method never performed much worse. Figure shows that the N n 0 window method would never perform much worse, and would often perform substantially a All values in kcal mol -1 . Uncertainties are 95 % confidence intervals obtained by bootstrapping over 10000 iterations with replacement.