Molecular mechanics with fluctuating atomic charges - a new force field with a semi-empirical charge calculation

A new force field has been designed to implement the calculation of Coulomb interactions with fluctuating atomic charges. The charges are calculated b y use of a semi-empirical quantum chemical method bond polarization theory (BPT). The BPT method establishes a direct proportionality between molecula r properties, for instance atomic charges or chemical shifts, and bond pola rization energies. These energies are calculated from bond orbitals that ar e constructed for every bond of the force field. Thus the charges depend on the three-dimensional geometry of the molecular system, and it is possible to include all mutual polarizations in the term for electrostatic interact ion. The primary goal of this new force field is better description of the intermolecular interactions of molecular systems. No special term within th e force field is applied for the description of hydrogen bonds. The inclusi on of the polarization effect over the whole system is one of the most impo rtant advantages of the method in respect of force fields that divide the m olecular system into molecular mechanics and quantum chemical regions. The force field was tested by being used to describe the structure and inte raction energies of several small molecular systems (26 hydrogen-bonded dim ers) from a web-based ab initio data collection by Halgren. The results sho w an overall RMS deviation of 2.5 kcal mol(-1) for the interaction energies , 0.06 Angstrom for the hydrogen bond distances (X...Z) and 20.1 degrees fo r the X-H...Z angles. This is comparable with most existing force fields. T he results were obtained with the original parametrization of Halgren for t he van der Waals interactions without any fine tuning of the interaction pa rameters. Additional interaction energies and structures of selected DNA/RNA base pai rs (see Figure) were studied. The geometries of hydrogen bonds, in particul ar, are reproduced satisfactorily - after geometry optimization the distanc es differ on average by 0.06 Angstrom and in the angles by 6 degrees from t he ab initio Hartree-Fock results including correlation.