title: Role of Solvent Dynamics in Stabilizing the Transition State of RNA Hydrolysis by Hairpin Ribozyme.
abstract: Structural and mechanistic studies of the hairpin ribozyme have been actively pursued over the last two decades to understand its catalytic strategy for RNA hydrolysis. Based on molecular dynamics simulations with the newly developed force field parameters for a vanadium-oxygen complex, we investigate the dynamic properties of the hairpin ribozyme in complex with a transition state analogue for the phosphodiester cleavage. The results indicate that the three nucleobases of the hairpin ribozyme (G8, A9, and A38) stabilize the negatively charged oxygen atoms in the transition state through the formation of five hydrogen bonds, which is consistent with the X-ray crystallographic data. In addition to the three catalytic nucleobases, several solvent molecules are also found to contribute to the catalytic action of the hairpin ribozyme by hydrogen bond stabilization of the negatively charged oxygens as well as by optimally positioning the catalytic nucleobases in the active site.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Korea, and Department of Chemistry, Seoul National University, Seoul 151-747, Korea.
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Korea, and Department of Chemistry, Seoul National University, Seoul 151-747, Korea.
authors.forename: Sangyoub
authors.initials: S
authors.lastname: Lee