In this study, we have proposed a way to alleviate this issue in a simple way -by introducing an empirical correction term named the "protein conformational free energy" and denoted as "∆G prot conf ". However, the problem is that it relies on pre-determined reference free energies (in our case, experimental ∆G) and cannot be applied prospectively when no reference data is available. Therefore, it is of limited applicability when accurate free energies are desired; ranking can still be obtained correctly, but not the absolute ∆Gs. On the contrary, if an accurate ABFE prediction is not required, then approximate methods such as ESMACS can produce a reliable ranking with substantially less computational effort.