Two docking poses (Supporting Figure ) at this binding site were found for the last ligand analyzed (134115849), both with a docking score of 6.2 kcal/mol. These afforded much more stable binding than observed with any of the previous ligands. One of the poses (Figure and S6) yielded remarkably stable interactions, whereas in triplicate simulations arising from the other pose one unbinding/rebinding event and one full unbinding were seen (Figure and Supporting Figure ). The relatively small size of the ligand allowed it to bend into several different conformations, all of which feature significant interactions between the cavity and the sulfoxide and nitro groups, with