Impact of DFT functionals on the predicted magnesium–DNA interaction: an ONIOM study

Abstract

We investigate the descriptions of several density functional theory functionals in modeling the interactions between DNA and magnesium, the divalent cation with the largest intracellular concentration. Precisely, the metal-induced proton transfer (PT) in the guanine-cytosine base pairs is analyzed within an hybrid two-layers QM/QM approach (ONIOM) by combining several functionals: BP86, B3LYP, B97-D, ωB97x-D and M06-2X, as well as the MP2 approach. The aqueous environment is simulated through, on the one hand, explicit solvent molecules present in the first hydration shell and, on the other hand, the well-known polarizable continuum model for the effects of solvation beyond this first shell. Calculations with all methods indicate that the Mg2+ cation coordination to DNA promotes a single PT reaction from the guanine to the cytosine base, characterized by a low back-reaction barrier. M06-2X and ωB97x-D functionals provide consistent results for the simulation of PT reactions. These methods can be combined with B97-D functional in ONIOM partition for the description of the stacking effects.