Nearly all BACE-1 ligands of GC4 share a common substructure that is also found in several PDB structures. This substructure consists of a hydroxyl group attached to a short two-carbon aliphatic chain, followed by an amide. Based on publicly available BACE-1 structures, this substructure has a conserved binding mode, making several hydrogen bonds with the binding pocket. To exploit this information during the docking, we used the ligand in the PDB 4DPF as a template for the position of the common substructure of GC4 ligands. A biasing penalty was applied to three atoms: the hydroxyl oxygen, one of the carbons in the aliphatic chain and the nitrogen in the amide. This penalty increases linearly with the distance from the corresponding atom of the template structure. If this distance is below 1.2 Å, the biasing penalty is zero, and the output score corresponds to the original, unaltered AutoDock4.2 scoring function.