title: Understanding the kinetic mechanism of RNA single base pair formation.
abstract: RNA functions are intrinsically tied to folding kinetics. The most elementary step in RNA folding is the closing and opening of a base pair. Understanding this elementary rate process is the basis for RNA folding kinetics studies. Previous studies mostly focused on the unfolding of base pairs. Here, based on a hybrid approach, we investigate the folding process at level of single base pairing/stacking. The study, which integrates molecular dynamics simulation, kinetic Monte Carlo simulation, and master equation methods, uncovers two alternative dominant pathways: Starting from the unfolded state, the nucleotide backbone first folds to the native conformation, followed by subsequent adjustment of the base conformation. During the base conformational rearrangement, the backbone either retains the native conformation or switches to nonnative conformations in order to lower the kinetic barrier for base rearrangement. The method enables quantification of kinetic partitioning among the different pathways. Moreover, the simulation reveals several intriguing ion binding/dissociation signatures for the conformational changes. Our approach may be useful for developing a base pair opening/closing rate model.
authors.affiliation: Department of Physics, University of Missouri, Columbia, MO 65211; Department of Biochemistry, University of Missouri, Columbia, MO 65211; Informatics Institute, University of Missouri, Columbia, MO 65211;
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Physics, University of Missouri, Columbia, MO 65211; Department of Biochemistry, University of Missouri, Columbia, MO 65211; Informatics Institute, University of Missouri, Columbia, MO 65211; Department of Physics, Jianghan University, Wuhan, Hubei 430056, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Physics, University of Missouri, Columbia, MO 65211; Department of Biochemistry, University of Missouri, Columbia, MO 65211; Informatics Institute, University of Missouri, Columbia, MO 65211; chenshi@missouri.edu.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Chen
mesh_terms: D020029:Base Pairing; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D012313:RNA / Q000737:chemistry*; D059370:RNA Folding
chemical_list: D012313:RNA
keywords: RNA folding kinetics; conformational network; kinetic Monte Carlo; master equation; molecular dynamics