Given these constraints, it should be noted that if one is simply interested in ranking a set of ligands and does not bother about the accuracy of absolute ∆G values then there is no justification to invest extra computational effort in employing the Apo scheme, as is visible from the bottom panel of Figure . The accuracies are almost identical for the entire subset of 137 complexes with very similar MUEs and RMSEs whether the Apo or the Holo scheme is used. In fact, one might argue that approximate ABFE methods such as ESMACS , that provide reliable ranking with much less computation as compared to alchemical ABFE methods, are preferable in such cases.