Fig. 8. Sampling of χ1 and χ2 angles in classical MD simulations (∼ 500ns) starting with three different starting conformations of BACE1 (PDB ID: 1W50, 3TPL and 1SGZ differs in flap elevation and orientation of Tyr. For detail refer6). As one can see simulations starting with 1W50 and 3TPL only sampled gauche+ (G+) conformation. Whereas, simulation starting with 1SGZ only sampled trans (T) conformation. Metadynamics simulation with χ1 and χ2 order parameters did a enhanced sampling of the conformational space. Looking at apparent free energy values (z axis unit in kJ mol−1) tells us that in apo BACE1 the flap remains in dynamic equilibrium between gauche+ and trans conformations. Gauche− (G−) is the minor population which was stabilised by H-bond interaction between Tyr and Lys.
