It should be noted, however, that an apparent overestimation is observed for some of the compound pairs involving L30, making the predicted free energy differences larger than those from experiments. An MSE of -1.36 kcal/mol is obtained for the L30 subgroup, comparing with an MSE of 0.16 kcal/mol for the subgroup with compound L2 as the reference. The apparent overestimations are investigated further in the following sections.