Molecular dynamics simulations provide insight into how the conformational dynamics of the WPD-loops in the chimeras differ from the WT enzymes, and to the origins of their slower catalytic Focusing first on Chimera 7, our ΔRMSF data from our MD simulations demonstrate the flexibility/rigidity of the WPD-loops of Chimera 7 and WT PTP1B to be highly similar in their open conformations (Figure ). Likewise, our H-bonding analysis only identifies one major difference, which is the newly formed hydrogen bond (H-bond) between F182Q and D181 in Chimera 7. This new H-bond does not appear to notably alter the conformational dynamics or protein interaction network in PTP1B, however given its direct interaction with the catalytic acid/base, it may have an important electrostatic effect on both chemical steps of catalysis, as also suggested from our EVB simulations (Figure ). Chemical intuition would suggest that mutation to glutamine would increase the acidity of the catalytic aspartic acid by placing more negative change on the acid's oxygen atoms through a side chain H-bond. This would be expected to have a beneficial effect on the rate of the first step in which the WPD-loop acts as an acid. However, in the second (rate-limiting) step where the WPD-loop acts as a base, the decreased basicity on the aspartic acids' oxygen due to mutation of the adjacent residue to glutamine could ultimately result in an increased activation free energy, which would explain the decreased kcat values observed for Chimera 7 compared to the WT PTP1B. Indeed, our EVB simulations (Figure and Table )