a) Locations of CBA (as shown by a sphere corresponding to its
carboxylic atom) during two independent MD trajectories initiated either at the
orthosteric cavity (Run #1, left) or at the vestibule (Run #2, right). Green to
blue colors indicate simulation time evolution. b) Distance analysis between a
CBA oxygen atom and donor/acceptor groups of S111 (bottom of the cavity), and
Y201, H264, and R265 (forming the vestibule). In both simulations, CBA engages
opportunistic hydrogen bonds with residues forming the vestibule. Periods during
which CBA visits the vestibule are highlighted.