title: Double-Metal-Ion/Single-Metal-Ion Mechanisms of the Cleavage Reaction of Ribozymes:  First-Principles Molecular Dynamics Simulations of a Fully Hydrated Model System.
abstract: The role of metal cations (Mg(2+)) 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 Mg(2+) 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.
authors.affiliation: Institute of Physics, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan, Center for Biological Resources and Informatics, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, Yokohama 226-8501, Japan, Division of Frontier Research, Creative Research Initiative "Sousei", Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo 001-0021, Japan, and Research Institute for Computational Sciences, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Mauro
authors.initials: M
authors.lastname: Boero
authors.affiliation: Institute of Physics, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan, Center for Biological Resources and Informatics, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, Yokohama 226-8501, Japan, Division of Frontier Research, Creative Research Initiative "Sousei", Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo 001-0021, Japan, and Research Institute for Computational Sciences, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tateno
authors.affiliation: Institute of Physics, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan, Center for Biological Resources and Informatics, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, Yokohama 226-8501, Japan, Division of Frontier Research, Creative Research Initiative "Sousei", Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo 001-0021, Japan, and Research Institute for Computational Sciences, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Terakura
authors.affiliation: Institute of Physics, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan, Center for Biological Resources and Informatics, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, Yokohama 226-8501, Japan, Division of Frontier Research, Creative Research Initiative "Sousei", Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo 001-0021, Japan, and Research Institute for Computational Sciences, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oshiyama