For the self-docking in Stage 1b, the presence of correct binding site conformation in the receptor helped to improve our overall docking predictions. For example, we used the PDB structures 3DV5 and BA04 for cross-docking in Stage 1a and self-docking in Stage 1b respectively for the ligand BACE_4. There were subtle differences in the side-chain orientations of the residues Gln12, Leu30, Gln73, Asn233 and Arg235 in the two structures (Fig. ). Having the correct side-chain packing in the self-docking challenge improved the RMSD from 2.23 Å in Stage 1a to 0.87Å in Stage 1b.