Institute of Bioinformatics and Medical Engineering, School of Mathematics and Physics, Jiangsu University of Technology, Changzhou, Jiangsu, China.
Department of Applied Physics, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
Biophys J. 2019 Nov 5;117(9):1674-1683. doi: 10.1016/j.bpj.2019.09.017. Epub 2019 Sep 20.
RNA functions are often kinetically controlled. The folding kinetics of RNAs involves global structural changes and local nucleotide movement, such as base flipping. The most elementary step in RNA folding is the closing and opening of a basepair. By integrating molecular dynamics simulation, master equation, and kinetic Monte Carlo simulation, we investigate the kinetics mechanism of RNA helix-terminal basepairing. The study reveals a six-state folding scheme with three dominant folding pathways of tens, hundreds, and thousands of nanoseconds of folding timescales, respectively. The overall kinetics is rate limited by the detrapping of a misfolded state with the overall folding time of 10 s. Moreover, the analysis examines the different roles of the various driving forces, such as the basepairing and stacking interactions and the ion binding/dissociation effects on structural changes. The results may provide useful insights for developing a basepair opening/closing rate model and further kinetics models of large RNAs.
RNA 的功能通常受到动力学控制。RNA 的折叠动力学涉及全局结构变化和局部核苷酸运动，例如碱基翻转。RNA 折叠的最基本步骤是碱基对的关闭和打开。通过整合分子动力学模拟、主方程和动力学蒙特卡罗模拟，我们研究了 RNA 螺旋末端碱基配对的动力学机制。该研究揭示了一个六态折叠方案，具有三个主要折叠途径，折叠时间尺度分别为数十、数百和数千纳秒。整体动力学受到错误折叠状态的去捕获限制，总折叠时间为 10 秒。此外，该分析还检查了各种驱动力（如碱基配对和堆积相互作用以及离子结合/解离对结构变化的影响）的不同作用。研究结果可为开发碱基对打开/关闭速率模型以及大型 RNA 的进一步动力学模型提供有用的见解。
