Superpositions of ribbon representations of the area around the flap in ligand–BACE1 complexes with open flap conformations crystallizing in different space groups. For comparison, a BACE1 structure with a closed flap is displayed in each representation. (a) Superimposition of all of the BACE1 complexes that crystallized in space group P6122. The cyan and purple structures represent PDB entries 1w51 and 2q15, respectively. (b) Superimposition of structures belonging to space group C2221: PDB entries 3fkt (yellow), 3exo (blue), 2wjo (cyan) and our cocrystallized structure (green). (c) Superimposition of structures belonging to space group C121: PDB entries 1ym4 (green), 2a11 (purple), 2qu2, 2qu3, 2zdz, 3hw1, 3h0b, 3in3, 3ind, 3l3a, 3lhg and 3msj. (d) Superimposition of structures belonging to space group P212121: PDB entries 2vie (green), 3kmx, 3kmy, 3kn0, 3l5d, 3l5e, 3l5f and 3l59. (e) Superimposition of the three copies in the asymmetric unit of PDB entry 3hvg belonging to space group C2: chain A (green), chain B (cyan) and chain C (magenta). In all cases the inhibitors are displayed as stick models.