On the other hand, the presence of the hydroxide ion significantly disrupted the geometry of the active site, especially the inhibitor coordination with the zinc, due to a strong preference for the hydroxide for bridging the two zinc ions and the electrostatic repulsion with the negatively charged phosphate group as shown in Fig. (b) and in the SI Fig. . Interestingly, the active site with the hydroxide was not only different from the starting crystal structure but also experienced more flexibility as two distinct conformations were characterized with the RMSD and distance analysis (see the SI Fig. .). The zinc-zinc distance in the water simulations remains at (4.7 ± 0.2) Å, close to the distance of 4.45 Å from the crystal structure. In the hydroxide simulations, this distance is (3.6 ± 0.1) Å, which is significantly different from the crystal structure distance.