Modeling Structure, Stability, and Flexibility of Double-Stranded RNAs in Salt Solutions

Double-stranded (ds) RNAs play essential roles in many processes of cell metabolism. The knowledge of three-dimensional (3D) structure, stability, and flexibility of dsRNAs in salt solutions is important for understanding their biological functions. In this work, we further developed our previously proposed coarse-grained model to predict 3D structure, stability, and flexibility for dsRNAs in monovalent and divalent ion solutions through involving an implicit structure-based electrostatic potential. The model can make reliable predictions for 3D structures of extensive dsRNAs with/without bulge/internal loops from their sequences, and the involvement of the structure-based electrostatic potential and corresponding ion condition can improve the predictions for 3D structures of dsRNAs in ion solutions. Furthermore, the model can make good predictions for thermal stability for extensive dsRNAs over the wide range of monovalent/divalent ion concentrations, and our analyses show that the thermally unfolding pathway of dsRNA is generally dependent on its length as well as its sequence. In addition, the model was employed to examine the salt-dependent flexibility of a dsRNA helix, and the calculated salt-dependent persistence lengths are in good accordance with experiments.

双链（ds）RNA在细胞代谢的许多过程中起着至关重要的作用。了解双链RNA在盐溶液中的三维（3D）结构、稳定性和柔韧性对于理解其生物学功能非常重要。在这项工作中，我们进一步发展了我们先前提出的粗粒化模型，通过引入一种基于隐式结构的静电势来预测单价和二价离子溶液中双链RNA的3D结构、稳定性和柔韧性。该模型能够根据其序列对具有/不具有凸起/内部环的大量双链RNA的3D结构进行可靠预测，并且基于结构的静电势和相应的离子条件的引入可以改进对离子溶液中双链RNA的3D结构的预测。此外，该模型能够在较宽的单价/二价离子浓度范围内对大量双链RNA的热稳定性进行良好的预测，并且我们的分析表明双链RNA的热解链途径通常取决于其长度以及其序列。另外，该模型被用于检测双链RNA螺旋的盐依赖性柔韧性，并且计算出的盐依赖性持续长度与实验结果吻合良好。