For the chorismate mutase reaction catalyzed by PchB, an earlier computational study has been published by Xie et al. They report activation parameters of ∆G ‡ = 12.1 kcal mol -1 and T∆S ‡ = -1.0 kcal mol -1 and claimed that since their calculated enzyme activation entropy penalty is 1.6 kcal/mol smaller than that of the uncatalyzed reaction, the enzyme-catalyzed reaction is entropically driven. However, their reported activation free energy is also significantly lower than experimental values. In comparison to the enzyme-catalyzed reaction, we obtain activation parameters of ∆H ‡ = 20.9 and T∆S ‡ = -3.4 kcal mol -1 K -1 for the reference reaction in water, in excellent agreement with experiment. The enzyme-catalyzed reactions in BsCM and PchB thus show a significant reduction in the activation enthalpy, while reductions in the entropy penalty are much smaller. Hence, both from our calculations and experiment is can be concluded that the enzyme-catalyzed reactions are enthalpy driven, and not entropy driven as suggested by Xie et al. A better understanding of the difference in activation thermodynamics can be obtained from a breakdown of the energetics by analyzing the MD trajectories. Neglecting the small pressurevolume term, the activation enthalpy can be approximated by