The ligand binding site of BACE-1 is exposed to water, but, as is common in docking, we retained no ordered water molecules while docking. However, the active site of BACE-1 can either be wet or dry depending on the nature of the ligand . In order to capture any structural changes in the proteinligand complex, including changes in the water structure as different ligands bind, we simulated the selected binding poses from HYBRID in explicit solvent using molecular dynamics (MD) to have better conformational sampling. Ideally these simulations would also allow water to solvate the binding site and different ligands as is most suitable in each case.