The calculated activation and reaction free energies from our EVB calculations of the hydrolysis step catalysed by wild-type YopH and PTP1B (prior work ) as well as YopH Chimeras 2 and 3 are shown in Table and . As can be seen from this data, if anything, we obtain slightly lower calculated activation free energies for Chimeras 2 and 3 compared to what we obtain for the wild-type parent enzymes. This is similar to our prior work on PTP1B chimeras, where the small differences in predicted activation free energies from idealized closed conformations were inadequate to account for much larger differences in turnover numbers, in contrast to the much larger differences in loop dynamics between chimeras observed in our simulations . Experimental data is obtained from The raw data for this figure is presented in Table . Note that no experimental data is presented in panel A for Chimera 2, as this Chimera is catalytically inactive . (B) Electrostatic contributions of selected amino acids (∆∆G ‡ elec, kcal mol -1 ) to the calculated activation free energies for the hydrolysis steps catalyzed by WT-YopH and Chimeras 2 and 3. All electrostatic contributions were scaled assuming an internal dielectric constant of 4 . Data was obtained from the calculated EVB trajectories using the linear response approximation (LRA) and is represented as average and standard error of the mean over 30 individual trajectories per system. The amino acids that are directly participating in the reaction (the catalytic cysteine and aspartic acid) are not shown. Chimeras 2 and 3 carry a Q357F substitution. The corresponding raw data for this plot is presented in Table .