We have used empirical valence bond (EVB) simulations to model the rate-limiting hydrolysis step catalyzed by Chimeras 2 and 3, following from our prior simulation studies of PTP1B and YopH . We applied the same simulation setup, including equilibration and EVB simulations, as in our prior work , using the revised parameters provided in . EVB simulations were performed using the Q6 simulation package and the OPLS-AA force field, for consistency with our previous work . Each chimera was simulated for 30 replicas, using an initial 30 ns of equilibration starting from the approximate EVB transition state (λ = 0.5, Figure ). Production simulations were then propagated from the transition state to both reactants and products using 51 mapping windows in total, each with a simulation time of 200 ps. Simulation analysis was performed using CPPTRAJ .