Diffuse Ions Coordinate Dynamics in a Ribonucleoprotein Assembly
Diffuse Ions Coordinate Dynamics in a Ribonucleoprotein Assembly
复制标题
核糖核蛋白组装中的扩散离子协调动力学
DOI：
10.1021/jacs.2c04082
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发表时间：
2022
影响因子：
15
通讯作者：
Whitford, Paul C.
中科院分区：
文献类型：
--
作者：
Wang, Ailun;Levi, Mariana;Mohanty, Udayan;Whitford, Paul C.
适当的离子浓度是RNA和核糖核蛋白（RNP）组装的功能动力学所必需的。虽然实验和计算技术已经为螯合离子的性质提供了许多见解，但对于扩散离子对大规模构象重排的能量贡献知之甚少。为了解决这个问题，我们提出了一个模型，旨在量化扩散单价和二价离子对生物分子组装动力学的影响。该模型采用全原子（非氢）分辨率和显式离子，其中有效电位解释水化效应。我们首先表明，该模型准确地预测了原型RNA系统中过量Mg2+离子的数量，其水平与现代粗粒度模型相当。然后，我们将该模型应用于完整的核糖体，并展示了扩散Mg2+和K+离子之间的平衡如何控制tRNA分子在翻译过程中的动力学。该模型预测了扩散离子对与tRNA进入相关的自由能垒的不同影响，以及tRNA与核糖体结合的能量。总之，这一分析揭示了扩散离子对RNP组装动力学的直接影响。
Proper ionic concentrations are required for the functional dynamics of RNA and ribonucleoprotein (RNP) assemblies. While experimental and computational techniques have provided many insights into the properties of chelated ions, less is known about the energetic contributions of diffuse ions to large-scale conformational rearrangements. To address this, we present a model that is designed to quantify the influence of diffuse monovalent and divalent ions on the dynamics of biomolecular assemblies. This model employs all-atom (non-H) resolution and explicit ions, where effective potentials account for hydration effects. We first show that the model accurately predicts the number of excess Mg2+ions for prototypical RNA systems, at a level comparable to modern coarse-grained models. We then apply the model to a complete ribosome and show how the balance between diffuse Mg2+and K+ions can control the dynamics of tRNA molecules during translation. The model predicts differential effects of diffuse ions on the free-energy barrier associated with tRNA entry and the energy of tRNA binding to the ribosome. Together, this analysis reveals the direct impact of diffuse ions on the dynamics of an RNP assembly.