Another interesting observation is the effect of the size of the alchemical region (defined as the number of atoms in the alchemical region) on the accuracy and precision of the predicted ∆∆G values. As shown in a previous TIES study, the precision of predicted free energies decreases as the size of the alchemical region increases. On the other hand, the accuracy of such predictions remains relatively unaffected by this quantity. In the present study, we obtain consistent results. We pulled out all transformations with the sum of the appearing and disappearing atoms greater than 40 from the full dataset (a total of 40 transformations with the sum ranging from 41 to 68) and compared their |∆∆∆G| as well as σ T IES with the sum. The corresponding Pearson's ρ for these quantities are 0.18 ± 0.15 and 0.45 ± 0.18, respectively, further confirming the previous findings.