The reaction path for the rearrangement of chorismate to prephenate, catalyzed by chorismate mutase, has been calculated with ab initio quantum chemistry. The calculation of the reaction path is initiated from two catalytically competent conformations of the enzyme that are selected from an X-ray structure and from a snapshot of a molecular dynamics simulation leveraged from the X-ray structure. The quantum calculations employ effective fragment potentials (EFPs) to model the interaction of the protein active site with the substrate in the quantum Hamiltonian. The ability to leverage the X-ray structure into a range of protein conformations abstracted from molecular dynamics simulations to be further analyzed using ab initio methods is demonstrated. Ab initio optimized enzyme-substrate complexes for the oxabicyclic transition state analogue (TSA) and the product, prephenate, compare well with the X-ray structures. We predict the geometry of the active site complex with the reactant, chorismate, and the transition state for the pericyclic reaction. We identify two residues as critical to catalysis, glu78 and tyr108. Binding of the cyclohexadienyl ring's C4-OH substituent of chorismate to the carboxylate of glu78 activates the breaking ether bond. The tyr108 residue is essential in providing the appropriate orientation of the transition-state fragments within the active site to ensure that prephenate is formed. The calculated electronic activation energies for both enzyme conformations studied are lower than the reaction barrier obtained experimentally. The large kinetic isotope effect (KIE) for O-18 in the ether bond agrees qualitatively with the experimental value that suggests a very polarized transition state.