To the best of our knowledge, previously, only Michel et al. has performed ligand transformations by introducing intermediate states in free energy calculations that differ in the number of trapped waters. Specifically, Michel et al.'s work studied both ligands' binding modes with and without trapped waters. This study examined ABFEs of trapped water molecules using the double-decoupling formalism employing Monte Carlo (MC) simulations. For convergence, the authors localized the trapped water at its putative location in the binding site using a spherical hard-wall potential. In their simulations, the hard-wall potential forbade the trapped water from escaping its binding site and also restricted solvent water molecules from diffusing near the trapped water. However, the study did not take into account the free energy to remove the spherical hard-wall potential when the trapped water was in a fully interacting state. Such a contribution would essentially represent free energy of decoupling the trapped water in a preexisting solvent cavity. Moreover, the hard-wall potential only restrained the solvent water from diffusing into the binding site of the trapped water, and no such restraint was applied to the surrounding environment, e.g. the protein's side chains. This is important, because Ge et al. have shown that unrestrained protein side chains in such simulations can occupy the binding site of the trapped water after its decoupling, severely hampering the convergence of the simulations. The study of Michel et al. thus has important connections to our present work, but we cannot apply the same approach here -not only due to the issues above, but also because a hard-wall potential cannot be implemented in typical MD simulations, as MD simulations require computation of a force, which is infinite at the boundary of a hard-wall potential. Despite these limitations, the prior study sets an important precedent for our work.