Despite the overall topological similarities between the FES for each enzyme, however, important energetic differences are observed (Table ). With the exception of BurPL, the different FES suggest that conformers A and B in the S/I variants are nearly isoenergetic, in comparison to the energetic favorability of the B conformer in the H/F variant. Since the neighboring side chains, for these conformers, are almost the same for all organisms, this probably arises from subtle dynamical effects of the W-loop. Specifically, for LCC and TfCut, this change in the energetics of the FES is accompanied by reductions of 4.4 and 3.3 kcal/mol in the relative free energy difference between the B and A basins, respectively (Table ).