Furthermore, were the WPD-loop able to close normally, our EVB simulations predict the hydrolysis step of catalysis catalyzed by Chimera 1 to have a similar activation free energy to that of other Chimeras modeled here (Figure and Table ). It is possible, however, that dthe WPD-loop of Chimera 1 can adopt another conformation that is more favorable than the closed WPD-loop conformation (that is separated by a reasonably large energetic barrier), which would preclude it from being able to attain a catalytically competent loop-closed conformation.