RNA, a highly charged biopolymer composed of negatively charged phosphate groups, defies electrostatic repulsion to adopt well-defined, compact structures. Hence, the presence of positively charged metal ions is crucial not only for RNA's charge neutralization, but they also coherently decorate the ion atmosphere of RNA to stabilize its compact fold. This feature article elucidates various modes of close RNA–ion interactions, with a special emphasis on Mg²⁺ as an outer-sphere and inner-sphere ion. Through examples, we highlight how inner-sphere chelated Mg²⁺ stabilizes RNA pseudoknots, while outer-sphere ions can also exert long-range electrostatic interactions, inducing groove narrowing, coaxial helical stacking, and RNA ring formation. In addition to investigating the RNA's ion environment, we note that the RNA's hydration environment is relatively underexplored. Our study delves into its profound interplay with the structural dynamics of RNA, employing state-of-the-art atomistic simulation techniques. Through examples, we illustrate how specific ions and water molecules are associated with RNA functions, leveraging atomistic simulations to identify preferential ion binding and hydration sites. However, understanding their impact(s) on the RNA structure remains challenging due to the involvement of large length and long time scales associated with RNA's dynamic nature. Nevertheless, our contributions and recent advances in coarse-grained simulation techniques offer insights into large-scale structural changes dynamically linked to the RNA ion atmosphere. In this connection, we also review how different cutting-edge computational simulation methods provide a microscopic lens into the influence of ions and hydration on RNA structure and dynamics, elucidating distinct ion atmospheric components and specific hydration layers and their individual and collective impacts.

中文翻译：

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离子和水合气氛对 RNA 结构和动力学的影响：来自先进理论和计算方法的见解

RNA 是一种由带负电的磷酸基团组成的高电荷生物聚合物，能够克服静电排斥，形成清晰、紧凑的结构。因此，带正电的金属离子的存在不仅对于RNA的电荷中和至关重要，而且它们还一致地装饰RNA的离子气氛以稳定其紧凑的折叠。这篇专题文章阐明了 RNA-离子密切相互作用的各种模式，特别强调了 Mg ²⁺作为外球和内球离子。通过示例，我们重点介绍了内球螯合 Mg ²⁺如何稳定 RNA 假结，而外球离子也可以发挥长程静电相互作用，诱导凹槽变窄、同轴螺旋堆积和 RNA 环形成。除了研究 RNA 的离子环境之外，我们注意到 RNA 的水合环境相对而言还没有得到充分研究。我们的研究采用最先进的原子模拟技术，深入研究了它与 RNA 结构动力学的深刻相互作用。通过示例，我们说明特定离子和水分子如何与 RNA 功能相关，利用原子模拟来识别优先离子结合和水合位点。然而，由于涉及与 RNA 动态性质相关的大长度和长时间尺度，了解它们对 RNA 结构的影响仍然具有挑战性。尽管如此，我们的贡献和粗粒度模拟技术的最新进展提供了对与 RNA 离子气氛动态相关的大规模结构变化的见解。在这方面，我们还回顾了不同的尖端计算模拟方法如何为离子和水化对 RNA 结构和动力学的影响提供微观视角，阐明不同的离子大气成分和特定的水化层及其个体和集体影响。