Aspects of hybrid QM/MM calculations: The treatment of the QM/MM interface region and geometry optimization with an application to chorismate mutase

The location of stationary points on potential energy surfaces calculated by hybrid quantum mechanical (QM)/molecular mechanical (MM) methods, allowing for relaxation of both the QM and MM regions, is discussed and illustrated with results from a study of the enzyme chorismate mutase. Enhanced interactions between carboxylate groups and neighboring arginine residues are shown to be important in the catalysis of chorismate to prephenate by this enzyme. The treatment of the interface between the QM and MM regions is studied by calculations on a series of models of amino acids.