The docking procedure identified two possible binding poses at this site, with similar but modest docking energies (-6.1 and -5.7 kcal/mol). None of these poses was found to be stable upon molecular dynamics simulation: the ligand spontaneously left the crevice after a few nanoseconds, and eventually associated elsewhere at the protein surface, far from the initial binding pose in both cases (Supporting Figure ). Interestingly, in the second simulation the ligand did associate with the active site itself during 30 ns (between 55 and 85 ns, Supporting Figure ), but that interaction was not stable enough to warrant further analysis. The second binding mode (Supporting Figure ) is not stable either: the cyclohexyl moiety initially lies in the 162-164 pocket, but the whole ligand leaves the site and rebinds in the opposite conformation, with the indole moiety in the 162-164 cavity (as in the second simulation originating from the best docking mode, Supporting Figure and). The third binding mode is also labile (Supporting Figure ), with one of the simulations yielding an unbinding/rebinding event that replaces the ligand in the original pocket (with the indole part in the 162-164 pocket and the cyclohexyl moiety in a quite different orientation from that obtained from the previous docking poses) and the second one yielding a complete separation of the ligand and its association at a very different point of the protein surface (Supporting Figure and). Overall, the simulations arising from the detected docking poses of this ligand show that its indole moiety has a moderate affinity for the pocket lined by aminoacids 162-164, but the interaction is not strong enough to overcome the tendency of the cyclohexyl moiety to establish relatively undiscriminating interactions with other portions of the protein surface. This result may, however, suggest that the inclusion of a 5-iodo-2,3-dioxoindol-1-yl moiety might be a fruitful strategy in the development of molecules targetting this binding pocket.