Prior simulation studies of TPI by both us and others have indicated that the large ligand-gated conformational change of the gripper loop 6 is correlated with smaller conformational motions in other decorating loops on the active site. We made similar observations when studying loop motions in PTP1B. However, as these simulations indicate, even studying the motion of one large dominating conformational change is computationally non-trivial, and the current systems involve the interdependent conformational rearrangements of multiple loops simultaneously. Our current simulations of HisA, PriA and TrpF (1) provide rich detail of the conformational behavior of the catalytic loops in the different systems, and (2) provide insight into the link between conformational dynamics, catalytic activity and functional evolution in the different enzymes, in particular the role of loops 1 and 5 in regulating PriA and HisA's activity and selectivity, as well as the gripper loops 3 and 4 in driving ligand-gated conformational changes in these enzymes. This, in turn, is significant, because in recent years, there has been substantial (and increasing) interest in exploiting techniques such as loop grafting and related approaches in order to engineer flexible loops in enzymes as a means of controlling their catalytic activity. Our data provide clear evidence that this is likely to be a powerful strategy for artificially manipulating the diverse catalytic repertoire 47 of TIM-barrel proteins.