Optimization of quantum mechanical molecular mechanical partitioning schemes: Gaussian delocalization of molecular mechanical charges and the double link atom method

Abstract

Two new techniques for modeling chemical processes in condensed phases with combined quantum mechanical and molecular mechanical (QM/MM) potentials are introduced and tested on small, model compounds. The first technique, the double link atom (DLA) method, is an extension of the traditional, single link atom (SLA) method to avoid some of the problems with the latter method. These problems are primarily electrostatic, as the SLA method can produce an unphysical overall charge or dipole. The second technique, the delocalized Gaussian MM charge (DGMM) method, is an empirical way to include the delocalized character of the electron density of atoms in the MM region. This can be important for the electrostatic interaction of the QM region with nearby atoms in the MM region, and it can simplify the rules governing which classical interactions are included in the energies and forces. Even for very short distances, the DGMM method does not require the neglect of the MM host in the QM calculation. The DGMM method can be used for modeling reactions in solution, and it can be combined with methods such as the link atom, frozen orbital, or pseudopotential methods for terminating the QM region at a covalent bond. The DLA and the DGMM methods have been combined effectively. Presented here are tests on small, model systems that mimic properties important for reactions in proteins, in particular rotational barriers, proton affinities, and deprotonation energies. The new methods yield improved energetics for model compounds, vis-à-vis a point-MM-charge and SLA treatment.