Calculations of magnesium-nucleic acid site binding in solution

The interaction of nucleic acids with metal cations, particularly magnesium, plays an important role in stabilizing their tertiary structure. An accurate quantitative description of these interactions requires high-level quantum chemical calculations. Because metal-nucleic acid interactions occur in water, solvation effects are important. To explore the influence of solvent we calculated the interaction energies of guanine and the dimethyl phosphate anion with a hexahydrated magnesium ion, which represent the main binding modes of magnesium and nucleic acids. We used density functional theory within the CPCM model and compared these results with data obtained for these complexes using the GBSA and PB approaches with the AMBER ff99 force field. The comparison indicates that the empirical force field significantly underestimates the total interaction energy and that the main source of error is an inaccurate description of the gas-phase interaction term. The presence of charge transfer and polarization contributions in the latter leads to a contraction of the complex geometry relative to that predicted by the classical potential. This lack increases the error in the nuclear-centered-charge approximation of the electrostatic energy. A method to calculate total interaction energies applicable for large systems in solution is proposed.