The results from a combined QM/MM study of the reaction catalyzed by Bacillus subtilis Chorismate Mutase are presented. Chorismate Mutase catalyzes the skeletal rearrangement of chorismate to prephenate with a 2 x 10(6) rate acceleration over the solution phase reaction. Chorismate Mutase does not chemically catalyze the reaction but selectively chooses a destabilized conformer of chorismate. The simulation is consistent with previous structural studies insofar as the enzyme does not chemically catalyze the reaction. It is found that the minimum energy enzyme-substrate complex has chorismate in a distorted geometry relative to the ground state structure in the gas phase. The pyruvyl sidechain has rotated to maximize the interactions in the active site with the result that the distance between the reaction centers is shorter. In addition it is shown that the enzyme preferentially binds the transition state with the biggest interactions being due to Arg90 and Glu78. Thus the catalysis of chorismate may be rationalized in terms of a combination of substrate strain and transition state stabilization.