The present MC/MD method achieves speedups of 10-1000x over our prior version by using a parallel MC algorithm that is effectively ported to the GPU. A further update allows it to support all simulation box types by defining the steric grid not in terms of the boundary but in terms of the distances from a molecular component of interest, such as a ligand or a residue at the edge of a binding pocket. The ability to equilibrate buried water molecules with minimal slowdown means this can be integrated with alchemical free energy calculations and performed as part of any system setup to establish preferred locations of water molecules. This is important as it solves the need for a priori knowledge regarding the hydration state of the cavity and allows for water sampling in the context of a flexible protein. It may also find application for structural optimization of water molecules in crystallographic or cryo-electron microscopy structures, and to accelerate sampling of structural processes that involve the penetration of water into the protein interior, potentially including protein conformational changes or full denaturation. It may be thought that the acceptance rate would be higher for GCMC than for the present MC method, because a trial move for GCMC does not require paying the penalty of removing water from its initial location. In fact, this should not be the case, as the acceptance probability for a move to a given location with GCMC should be the same as the mean acceptance probability to the same location from a simulation of bulk water having the same chemical potential as that used in the GCMC calculation.