In order to compare the performance of Q-RepEx against conventional EVB simulations, we applied the Q-RepEx protocol shown in Figure to three previously studied enzymes. The first of these (Figure ), triosephosphate isomerase (TPI), is a tremendously proficient catalyst of the reversible isomerization of D-glyceraldehyde-3-phosphate (GAP) to dihydroxyacetone phosphate (DHAP). TPI is activated by a large ligand-gated conformational change, in which a key catalytic loop, loop 6, moves ~7 Å from a catalytically inactive open conformation to a catalytically active closed conformation, thus closing over the active site and sequestering it from solvent .