QM-MM Investigation of the Reaction of Peroxynitrite with Carbon Dioxide in Water

We have investigated the reaction of peroxynitrite with carbon dioxide in aqueous solution by means of combined quantum-classical (QM-MM) molecular dynamics simulations. In our QM-MM scheme, the reactant was modeled using density functional theory with a Gaussian basis set, and the solvent was described using the mean-field TIP4P force field. The free energy profile of this reaction has been computed using umbrella sampling and multiple steering molecular dynamics (MSMD) schemes. Umbrella sampling methods turned out to be much more efficient than MSMD schemes, due to the possibility of employing a combination of classical and QM-MM thermalization schemes. We found the presence of a significant barrier in the free energy profile associated with the reaction in solution, which is not present in vacuum, that may be ascribed to the significant charge redistribution upon reaction and the concomitant solvation pattern changes.