Combined Electrostatically Embedded Multiconfiguration Molecular Mechanics and Molecular Mechanical Method: Application to Molecular Dynamics Simulation of a Chemical Reaction in Aqueous Solution with Hybrid Density Functional Theory.

We here combine the electrostatically embedded multiconfiguration molecular mechanics (EE-MCMM) method for generating global potential energy surfaces in the presence of an electrostatic potential with molecular mechanics (MM). The resulting EE-MCMM/MM method is illustrated by applying it to carry out a molecular dynamics simulation for the symmetric bimolecular reaction Cl(-) + CH3Cl' → ClCH3 + Cl'(-) in aqueous solution with hybrid density functional theory as the quantum mechanical level. The potential of mean force is calculated, and the free energy barrier is found to be 25.3 kcal/mol, which is in good agreement with previous work. The advantage of the combined EE-MCMM and MM method is that the number of quantum mechanical calculations required for the active subsystem is very small compared to straight direct dynamics.