We opted to include explicit water in our model system so as to better represent the typical solvated state of biological systems. We also sought to evaluate whether this method is viable in a solvated system; while previous BLUES ligand rotations were carried out in an explicitly solvated system, 15 the ligand itself is buried in a binding pocket mostly devoid of local solvent molecules. Further, in recent work, others have encountered challenges when per- forming rotational moves on valine and methionine sidechains in explicit solvent using a hybrid MD and NCMC approach, providing an opportunity to see whether the approach employed here might fare better.