Finally, we demonstrate that although the WPD-loop may appear to be a simple decorating loop that positions a key catalytic residue, in fact, changes in one part of the protein (substitutions on this loop) affect dynamics of other parts of the protein (e.g. the coupled dynamics of the E-loop and loop 11). Such coupled dynamics can be exploited in protein engineering, through the introduction of mutations distal to the active site, that can shift the overall conformational ensemble of the protein, including potentially controlling the dynamics of key catalytic loops. This is also significant in light of increased awareness of the role of the dynamics of decorating loops in the natural evolution of enzyme function, and the potential of altering loop dynamics and loop grafting as a powerful tool in protein design. Here, we demonstrate that non-catalytic loop residues are potential mutational targets for manipulating the conformational equilibria of key catalytic loops in PTPs, in addition to analogous effects from mutation of allosteric residues.