Max-Born-Institut für Nichtlineare Optik und Kurzzeitspektroskopie, Berlin 12489, Germany.
Chem Commun (Camb). 2021 Dec 3;57(96):12880-12897. doi: 10.1039/d1cc05367a.
The structure and dynamics of polyanionic biomolecules, like RNA, are decisively determined by their electric interactions with the water molecules and the counterions in the environment. The solvation dynamics of the biomolecules involves a subtle balance of non-covalent and many-body interactions with structural fluctuations due to thermal motion occurring in a femto- to subnanosecond time range. This complex fluctuating many particle scenario is crucial in defining the properties of biological interfaces with far reaching significance for the folding of RNA structures and for facilitating RNA-protein interactions. Given the inherent complexity, suited model systems, carefully calibrated and benchmarked by experiments, are required to quantify the relevant interactions of RNA with the aqueous environment. In this feature article we summarize our recent progress in the understanding of the electrostatics at the biological interface of double stranded RNA (dsRNA) and transfer RNA (tRNA). Dimethyl phosphate (DMP) is introduced as a viable and rigorously accessible model system allowing the interaction strength with water molecules and counterions, their relevant fluctuation timescales and the spatial reach of interactions to be established. We find strong (up to ≈90 MV cm) interfacial electric fields with fluctuations extending up to ≈20 THz and demonstrate how the asymmetric stretching vibration (PO) of the polarizable phosphate group can serve as the most sensitive probe for interfacial interactions, establishing a rigorous link between simulations and experiment. The approach allows for the direct interfacial observation of interactions of biologically relevant Mg counterions with phosphate groups in contact pair geometries the rise of a new absorption band imposed by exchange repulsion interactions at short interatomic distances. The systematic extension to RNA provides microscopic insights into the changes of the hydration structure that accompany the temperature induced melting of the dsRNA double helix and quantify the ionic interactions in the folded tRNA. The results show that pairs of negatively charged phosphate groups and Mg ions represent a key structural feature of RNA embedded in water. They highlight the importance of binding motifs made of contact pairs in the electrostatic stabilization of RNA structures that have a strong impact on the surface potential and enable the fine tuning of the local electrostatic properties which are expected to be relevant for mediating the interactions between biomolecules.
多阴离子生物分子（如 RNA）的结构和动力学，主要由它们与环境中的水分子和抗衡离子的电相互作用决定。生物分子的溶剂化动力学涉及非共价和多体相互作用的微妙平衡，以及由于热运动而导致的结构波动，这些波动发生在飞秒到亚纳秒的时间范围内。这种复杂的波动多粒子情况对于定义具有深远意义的生物界面的特性至关重要，这些特性对于 RNA 结构的折叠和促进 RNA-蛋白质相互作用至关重要。鉴于其固有的复杂性，需要合适的模型系统，并通过实验进行仔细的校准和基准测试，以量化 RNA 与水相环境的相关相互作用。在这篇专题文章中，我们总结了我们在理解双链 RNA（dsRNA）和转移 RNA（tRNA）生物界面静电学方面的最新进展。二甲基磷酸酯（DMP）被引入作为一个可行且严格可访问的模型系统，允许确定与水分子和抗衡离子的相互作用强度、它们的相关波动时间尺度以及相互作用的空间范围。我们发现具有强烈的（高达≈90 MV cm）界面电场，波动延伸至≈20 THz，并展示了如何极化磷酸基团的不对称伸缩振动（PO）可以作为界面相互作用的最敏感探针，在模拟和实验之间建立严格的联系。该方法允许直接观察生物相关 Mg 抗衡离子与处于接触对几何形状的磷酸基团的界面相互作用，在短原子间距离处，由于交换排斥相互作用而出现新的吸收带。系统地扩展到 RNA，为温度诱导 dsRNA 双螺旋熔化时伴随的水合结构变化提供了微观见解，并量化了折叠 tRNA 中的离子相互作用。结果表明，带负电荷的磷酸基团对和 Mg 离子对是嵌入水中的 RNA 的关键结构特征。它们强调了由接触对组成的结合基序在 RNA 结构静电稳定化中的重要性，这对表面电位有强烈影响，并能够微调局部静电特性，这有望在介导生物分子之间的相互作用中发挥作用。
