Protein and Ligand Preparation. X-ray complexes were prepared using the Schrödinger Protein Preparation Wizard. In cases where residues with absent side-chain atoms were detected, they were filled using Prime. PROPKA was used to define the protonation states at pH 7, except for BACE1, which were determined at pH 5 matching the acidic pH used in the bioassays. Ligand Docking. MCS docking used the GLIDE software that requires a preprepared docking grid that was calculated using default settings specifying the crystallized ligands as the grid center.