RNA双螺旋结构的柔性及其中离子效应的研究

RNAs are important biological macromolecules. RNAs would exhibit strong conformation fluctuations in solutions rather than keep their static structures. Double-stranded (ds) helix is a fundamental structural segment of RNAs. Flexibility of dsRNA helices plays an important role in their biological functions such as protein recognition and gene regulation. RNAs are highly charged polyanionic molecules, and metal ion binding is critical for the flexibility of RNAs, especially multivalent ions such as Mg2+. However, due to the coupling between conformational fluctuation and ion binding and the strong correlation between multivalent ions, there is lack of a comprehensive understanding on the flexibility of dsRNA and the ion effect. In this project, we will continuously develop the coarse-grained (Efold) model for predicting RNA 3D structure which was proposed previously by us. The refined Efold model, the all-atomistic molecular dynamics, the worm-like chain model and the tightly bound ion model will be combined together to study the flexibility of dsRNA helices and the ion effect, as well as the effects of loop, temperature and sequence. Our predictions will be compared with the available experiments and those for dsDNA helices, and we will further reveal the important factors in the flexibility of dsRNA helices and the relevant mechanism. This project would enable the comprehensive understanding on the flexibilities of dsRNA and dsDNA helices.

RNA是重要的生物大分子，其在生物体内并不是保持静态结构而是具有强的结构涨落。RNA双螺旋是基本的结构单元，其柔性在其生物功能中起着重要作用。RNA链上带有高密度负电荷，因而溶液中金属离子对其柔性有重要影响，特别是高价离子如Mg2+。然而，由于RNA的结构涨落与离子凝聚间的耦合以及高价离子间的强关联作用，对于RNA双螺旋的柔性及其中离子效应（特别是高价离子效应）的认识还较为肤浅。本项目中，我们将发展我们先前建立的粗粒化RNA三维结构预测（Efold）模型，并结合全原子分子动力学、蠕虫链模型和紧束缚离子模型等方法全面深入研究RNA双螺旋的柔性及其中的离子效应，并将与DNA双螺旋的柔性进行全面对比，进一步将研究中间环、温度和序列对RNA双螺旋柔性的影响，我们的预测将与相关实验比较，进而揭示RNA双螺旋柔性中的重要影响因素及其机制。本项目将促进对RNA双螺旋以及DNA双螺旋的柔性的全面理解。

RNA是非常重要的生物大分子，其功能与结构以及结构柔性紧密相关，由于RNA带有高密度的负电荷，离子结合对于RNA结构、柔性、热力学均至关重要。本项目围绕RNA双螺旋的柔性及其中的离子效应展开了全面深入和拓展的研究。此项目中，我们发展先前建立的粗粒化RNA三维结构预测（Efold）模型，并结合全原子分子动力学、蠕虫链模型和紧束缚离子模型等方法全面深入研究了RNA双螺旋的柔性及其中的离子效应，并与DNA双螺旋的柔性进行了全面对比，相关预测与相关实验进行了比较，进而揭示RNA双螺旋柔性中的重要影响因素及其机制。本项目基本按计划执行，取得了系列相关重要的进展。项目已发表在SCI刊物发表研究论文16篇，包括本领域重要刊物RNA、Biophys J、Plos Comput Biol论文9篇，并有后续成果在投寄和在准备中，项目主持人是上述所有论文的通讯作者。