Even after including the solvent restraint in our thermodynamic cycle, re-hydration may still be observed along edge G, which turns off the solvent repulsion to correctly account for its effect. A re-hydration along edge G would invalidate the ABFE thermodynamic cycle, since we are aiming to calculate the free energy of removing the trapped water. Releasing the position restraints along edge F allows the pocket to adapt to the absence of the trapped water, and might inhibit re-hydration. If re-hydration systematically occurs even after the system had time to rearrange, we consider the system to be unsuited for calculation of the ABFE of water using our method. One possible explanation of such behavior is that the water is less slow than initially assumed and that its binding and unbinding may be accessible to equilibrium simulations. In such cases, water sampling should be handled in conjunction with the free energy simulations themselves, rather than separated out as in the present work.