The ligand protonation states for the query ligands were calculated at pH 4.5 using pKa Plugin from ChemAxon and the Hydrogen atoms were added using Chimera 1.12 . Out of the 20 ligands, BACE_1, BACE_17, BACE_18, BACE_-19, and BACE_20 were modeled as neutral. The remaining 15 ligands had a charge of +1. We generated 1000 conformations for each ligand using OMEGA 3.0.8 (Open-Eye Scientific Software). We next docked the target ligand into its corresponding receptor structure(s) using HYBRID 3.2.0.2 with a docking resolution of 1.0 Å. The receptor was treated as a rigid structure during docking.