RNA“接吻”复合体的空间结构及其稳定性的预测

RNA“接吻”复合体结构不仅是一类非常典型的RNA三级结构单元，而且还具有极其重要的生物功能。研究其空间结构及其稳定性对于理解其功能机理，预防和治疗相关疾病有重要的意义。本项目将通过发展我们先前建立的空间结构预测模型，实现基于序列的RNA“接吻”复合体空间结构及其稳定性的预测。基于发展的粗粒化RNA结构模型并结合全原子分子动力学模拟，本项目将系统地研究RNA序列及所处溶液的离子环境等对RNA“接吻”复合体结构稳定性的影响，并且预测结果将与广泛的实验进行对比，以揭示其中的序列和离子效应。此外，本项目还将采用全原子分子动力学方法从原子层次研究该类复合体中“接吻”区域的局部结构涨落，并通过分析复合体中的氢键相互作用和其周围的离子分布揭示序列/离子对其稳定性影响的微观机制。本项目在推动RNA结构预测模型和方法发展的同时，还将加深人们对RNA三级结构折叠及其微观机制的理解。

RNA kissing complexes are not only the typical motifs of RNA tertiary structures, but also biologically important in lots of life processes. The knowledge of the spatial structures and dynamics of RNA kissing complexes is a fundamental prerequisite to completely understand their functions, and the related researches could be helpful in preventing and treating the relevant diseases. In this project, we will continuously develop the coarse-grained model proposed previously by us to predict the 3D structure and stability of RNA kissing complexes from their sequences. Based on the developed model and all-atom molecular dynamics simulations, we will systematically study the effects of sequence and salt on the stability of RNA kissing complexes, and the predicted results will be compared with the available experiments. Furthermore, we will use all-atom molecular dynamics simulations to study the local structure fluctuation and we will further reveal the microscopic mechanisms of salt/sequence effects in the stability of RNA kissing complexes by analyzing hydrogen bonding interactions and ion distributions. This project would be of benefit to the development of models and methods for RNA 3D structure prediction, and it could also enhance the understanding of the microscopic mechanisms of RNA tertiary structure folding.