We use quantum mechanics/molecular mechanics (QM/MM) calculations to estimate the activation free energy for the chemical reaction catalyzed by catechol O-methyltransferase. While in many cases the activation free energy of a chemical process is directly determined by the potential of mean force associated with a particular reaction coordinate, here we have included several corrections that have been proposed in the literature. These include the free energy change associated with release of the reaction coordinate motion in the reactant state, consideration of the curvilinear nature of the reaction coordinate, and correction due to the classical treatment of molecular vibrations. In addition, since potentials of mean force are usually obtained from low levels of QM theory to describe the quantum subsystem, we have included an interpolated correction term to improve this description at small additional cost. This last correction term has a dramatic effect, improving the agreement between the theoretical predictions and the experimental value, while the other terms considered make only small contributions to this particular reaction.