Mapping Interaction Energies in Chorismate Mutase with the Fragment Molecular Orbital Method

The Claisen rearrangement of chorismate to prephenate is mapped across the entire reaction pathway using the fragment molecular orbital (FMO) method. Three basis sets (6-31G(d), cc-pVDZ, and pcseg-1) are studied to provide guidance toward obtaining high accuracy with the FMO method on such systems. Using a fragmentation scheme of one residue per fragment, the FMO method using the 6-31G(d) basis set and second-order Møller-Plesset perturbation theory (MP2) with the hybrid orbital projection fragmentation scheme provides the most reliable results across the entire reaction pathway. Calculations using the multilayer FMO method are performed and shown to be in agreement with single-layer calculations in all cases with differences of less than one kilocalorie per mole for all tested basis set combinations along the entire reaction path. The use of restricted Hartree-Fock for the lower-level layer and MP2 for the higher-level layer gives the most consistent results when using the same basis set for both layers. Pair interaction energy decomposition analysis calculations confirm that electrostatic interactions are the predominant force between three key arginine residues and chorismate and that dispersion and charge transfer interactions in the binding pocket also play a role in the local chemistry of the reaction.