Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas, USA.
Biophys J. 2012 Feb 22;102(4):819-28. doi: 10.1016/j.bpj.2012.01.013. Epub 2012 Feb 21.
RNA molecules play critical roles in many cellular processes. Traditionally viewed as genetic messengers, RNA molecules were recently discovered to have diverse functions related to gene regulation and expression. RNA also has great potential as a therapeutic and a tool for further investigation of gene regulation. Metal ions are an integral part of RNA structure and should be considered in any experimental or theoretical study of RNA. Here, we report a multidisciplinary approach that combines anomalous small-angle x-ray scattering and molecular-dynamics (MD) simulations with explicit solvent and ions around RNA. From experiment and simulation results, we find excellent agreement in the number and distribution of excess monovalent and divalent ions around a short RNA duplex. Although similar agreement can be obtained from a continuum description of the solvent and mobile ions (by solving the Poisson-Boltzmann equation and accounting for finite ion size), the use of MD is easily extended to flexible RNA systems with thermal fluctuations. Therefore, we also model a short RNA pseudoknot and find good agreement between the MD results and the experimentally derived solution structures. Surprisingly, both deviate from crystal structure predictions. These favorable comparisons of experiment and simulations encourage work on RNA in all-atom dynamic models.
RNA 分子在许多细胞过程中发挥着关键作用。RNA 分子传统上被视为遗传信使,但最近发现它们具有与基因调控和表达相关的多种功能。RNA 作为一种治疗方法和进一步研究基因调控的工具也具有很大的潜力。金属离子是 RNA 结构的一个组成部分,在任何关于 RNA 的实验或理论研究中都应该考虑到它们。在这里,我们报告了一种多学科的方法,该方法结合了异常小角 X 射线散射和分子动力学(MD)模拟以及 RNA 周围的显式溶剂和离子。从实验和模拟结果来看,我们发现短 RNA 双链周围的单价和二价过剩离子的数量和分布非常吻合。尽管可以通过连续体描述溶剂和可移动离子(通过求解泊松-玻尔兹曼方程并考虑有限的离子大小)获得类似的一致性,但 MD 的使用很容易扩展到具有热波动的灵活 RNA 系统。因此,我们还对一个短的 RNA 假结进行了建模,并发现 MD 结果与实验得出的溶液结构之间存在良好的一致性。令人惊讶的是,两者都与晶体结构预测结果不符。这些实验和模拟的良好比较鼓励在全原子动力学模型中进行 RNA 研究。