Many of the chimeric offspring were inactive and/or insoluble, and those that were active showed reduced catalytic activities compared to that of either parent enzyme, despite conserved mechanisms and transition states . Structural and computational characterization indicated that the catalytically active PTP1B chimeras maintained backbone structural integrity and were able to sample both open and closed conformations of the WPD-loop, but with significant differences among them in the conformational space sampled . The dynamics of the open WPD-loop are particularly complex, with the loop sampling multiple metastable and interconverting conformations. Furthermore, while empirical valence bond (EVB) simulations ) indicated a chemical component to observed differences in turnover number, these were not substantial enough to account for the much larger observed effects (compared to differences in calculated activation free energies ).