Catalytic role of metal ion in the selection of competing reaction paths: A first principles molecular dynamics study of the enzymatic reaction in ribozyme

By using finite temperature first principles molecular dynamics, the mechanism of the enzymatic reaction of ribozyme was investigated for both the anionic and the radical charge states of the modeled RNA fragment. In the case of the anionic system, a pseudorotation and the subsequent 3' --> 2' migration occur in a vacuum, rather than the self-cleavage of the phosphodiester. On the other hand, when either a divalent metal ion (Mg2+) catalyst or the continuous hydrogen bond network of the solvent is present, the reaction path of the anionic species changes dramatically, going toward the transesterification channel. In a radical system, the transesterification can occur without a metal catalyst, as a consequence of the displacement of a hole (empty electronic state) along the reaction path. Thus, the present analysis suggests that a metal ion might be essential not only in lowering the activation barrier but also in selecting the reaction path among those corresponding to possible different charge states of the intermediate structure in vivo. Furthermore, simulation of the anionic species in solution shows that, in the absence of a metal catalyst, water molecules cooperate with the proton transfer via a proton wire mechanism and the hydrogen bond network plays a crucial role in preventing pseudorotations. On the other hand, when a metal cation is present in the vicinity of the site where the nucleophilic attack occurs, the hydrogen bond network is interrupted and detachment of the proton, enhanced by the catalyst, does not give rise to any proton-transfer process.