Double-metal-ion/single-metal-ion mechanisms of the cleavage reaction of ribozymes: First-principles molecular dynamics simulations of a fully hydrated model system

The role of metal cations (Mg2+) in the cleavage reaction of fully hydrated RNA enzymes is investigated via Car-Parrinello calculations. We find that the action of two metal catalysts is the most efficient way to promote, on one hand, the proton abstraction from O-2 '-H that triggers the nucleophilic attack and, on the other hand, the weakening and subsequent cleavage of the p-O-5 ' bond. The elimination of one of the two metal cations is shown to lead to an increase in the activation energy. Furthermore, we also find that an OH- included in the coordination shell of the Mg2+ close to O-2 ' promotes the initial proton abstraction and prevents its transfer to the ribozyme in both single- and double-metal-ion pathways, consistently with the experiment. This suggests that in real ribozyme systems, the double-metal-ion reaction mechanism in the presence of an OH- anion is favored with respect to single-metal-ion mechanisms.