In some cases, some water molecules may not be released by the ligand's binding, and these water molecules can localize in the binding site and can stabilize the protein-ligand complex by forming small water networks bridging protein residues and the ligand. Modifications of chemical groups on a ligand to displace these water molecules may sometimes lead to an optimized and highly selective ligand for the target protein, if the modified ligand can make favorable interactions in the binding site while displacing the localized waters. In molecular dynamics (MD) simulations, while the presence of such water molecules can strongly influence the binding free energies of protein-ligand complexes, their movement can sometimes be too slow to be adequately sampled during the course of the simulations. In a typical simulation, we can consider the movement of an interfacial water as slow if its unbinding and rebinding to its position in the protein's binding site cannot be sampled during the time scale of the simulation. This lack of unbinding and rebinding of a water can sometimes be due to physical barriers imposed by the surroundings, e.g. if the water's position is completely enclosed by protein and/or ligand atoms. However, even if a water is not restricted by its surroundings, but its exchange with the other solvent waters is very infrequent on the time scales of typical molecular simulations, it can be considered as a slow or "trapped" water, and its inadequate sampling can hamper the accuracy of the simulation.