All classical MD simulations were performed for holo and apo BSS models using the AMBER ff03 force field . The calculations were conducted with AMBER 18 according to the previously described protocol . The stable parts (i.e. final 20 ns) of the 50-60 ns simulation trajectories, i.e., exhibiting stable RMSD of the main chain (Fig. ), were analyzed with clustering using the k-means method taking into consideration heavy atoms of the active site residues (see SI).