Department of Physics, Wuhan University, Wuhan, China.
Biophys J. 2010 Apr 21;98(8):1617-25. doi: 10.1016/j.bpj.2009.12.4319.
We report a new computational approach to the prediction of RNA secondary structure folding kinetics. In this approach, each elementary kinetic step is represented as the transformation between two secondary structures that differ by a helix. Based on the free energy landscape analysis, we identify three types of dominant pathways and the rate constants for the kinetic steps: 1), formation; 2), disruption of a helix stem; and 3), helix formation with concomitant partial melting of a competing (incompatible) helix. The third pathway, termed the tunneling pathway, is the low-barrier dominant pathway for the conversion between two incompatible helices. Comparisons with experimental data indicate that this new method is quite reliable in predicting the kinetics for RNA secondary structural folding and structural rearrangements. The approach presented here may provide a robust first step for further systematic development of a predictive theory for the folding kinetics for large RNAs.
我们提出了一种新的计算方法来预测 RNA 二级结构折叠动力学。在这种方法中，每个基本动力学步骤都表示为两种二级结构之间的转换，这两种二级结构仅在螺旋上有所不同。基于自由能景观分析，我们确定了三种主要的途径和动力学步骤的速率常数：1）形成；2）螺旋茎的破坏；3）与竞争（不兼容）螺旋的部分熔融相伴的螺旋形成。第三种途径，称为隧穿途径，是两种不兼容螺旋之间转换的低势垒主要途径。与实验数据的比较表明，这种新方法在预测 RNA 二级结构折叠和结构重排的动力学方面非常可靠。这里提出的方法可能为进一步系统地开发用于大型 RNA 折叠动力学的预测理论提供了一个稳健的第一步。
