A strong point for our protocol was using ligand similarity for pose prediction. At the same time, it is also a limitation. Since BACE-1 inhibitors have been widely studied and there exists a substantial amount of deposited co-crystal structures of them, we were able to find reference ligands with very high molecular similarity to our query ligands in this work. Researchers might not have this edge for newly discovered protein targets or ligands with unique scaffolds. Methods like FRED , AutoDock Vina and Dock6 which do not require any reference ligand might be more wellsuited for those cases.