Free energy landscape and multiple folding pathways of an H-type RNA pseudoknot.
Free energy landscape and multiple folding pathways of an H-type RNA pseudoknot.
复制标题
H 型 RNA 假结的自由能景观和多重折叠途径
DOI：
10.1371/journal.pone.0129089
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Bian Y;Zhang J;Wang J;Wang J;Wang W
RNA序列如何折叠成特定的三级结构是理解其动力学和功能的关键问题之一。在这里，我们通过大规模的全原子分子动力学模拟和偏置交换元动力学来研究H型RNA假结的折叠过程。得到了折叠自由能图谱，并鉴定了几种折叠中间体。我们认为折叠是通过多种机制发生的，包括从第一个螺旋或第二个螺旋开始的分步机制，以及两个螺旋同时形成的协同机制。尽管具有多机制的性质，但从马尔可夫状态模型估计的系综折叠动力学是单指数的。研究还发现，金属离子的折叠和结合之间存在显著的相关性，结合离子在中间结构中起着长程相互作用的调节作用。在未折叠状态下，非天然相互作用占主导地位，也存在于一些中间体中，可能阻碍了RNA的折叠过程。
How RNA sequences fold to specific tertiary structures is one of the key problems for understanding their dynamics and functions. Here, we study the folding process of an H-type RNA pseudoknot by performing a large-scale all-atom MD simulation and bias-exchange metadynamics. The folding free energy landscapes are obtained and several folding intermediates are identified. It is suggested that the folding occurs via multiple mechanisms, including a step-wise mechanism starting either from the first helix or the second, and a cooperative mechanism with both helices forming simultaneously. Despite of the multiple mechanism nature, the ensemble folding kinetics estimated from a Markov state model is single-exponential. It is also found that the correlation between folding and binding of metal ions is significant, and the bound ions mediate long-range interactions in the intermediate structures. Non-native interactions are found to be dominant in the unfolded state and also present in some intermediates, possibly hinder the folding process of the RNA.
登录
查看更多内容
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
5.6
作者：
Cao, Song;Chen, Shi-Jie
通讯作者：
Chen, Shi-Jie
影响因子：
16.6
作者：
Hengesbach, Martin;Kim, Nak-Kyoon;Feigon, Juli;Stone, Michael D.
通讯作者：
Stone, Michael D.
影响因子：
3.3
作者：
Cossio, Pilar;Marinelli, Fabrizio;Pietrucci, Fabio
通讯作者：
Pietrucci, Fabio
影响因子：
4.4
作者：
Liu, Liang;Chen, Shi-Jie
通讯作者：
Chen, Shi-Jie