Insights into the structural stability of major groove RNA triplexes by WAXS-guided MD simulations
Insights into the structural stability of major groove RNA triplexes by WAXS-guided MD simulations
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DOI：
10.1016/j.xcrp.2022.100971
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发表时间：
2022-07-20
影响因子：
8.9
通讯作者：
Pollack, Lois
中科院分区：
文献类型：
--
作者：
Chen, Yen-Lin;He, Weiwei;Pollack, Lois
RNA三螺旋是常见的三级基序，与关键的生物学功能，包括信号转导。由于对它们的生物学重要性的认识是相对较新的，它们的全部结构特性尚未阐明。本文所述的溶液广角X射线散射（WAXS）与分子动力学（MD）模拟的结合，提供了一种新的方法来捕捉逃避晶体学表征的大沟RNA三链体的结构。这种方法产生测量和计算WAXS配置文件之间的良好协议，并允许这些图案的原子详细的可视化。使用相关图，定义的散射轮廓和RNA分子的真实的空间特征之间的关系，包括在双链RNA的第三条链的碱基三倍体的掺入后的微妙的构象变化。这种易于应用的方法有可能提供深入了解相互作用，稳定RNA三级结构，使功能。
RNA triple helices are commonly observed tertiary motifs that are associated with critical biological functions, including signal transduction. Because the recognition of their biological importance is relatively recent, their full range of structural properties has not yet been elucidated. The integration of solution wide-angle X-ray scattering (WAXS) with molecular dynamics (MD) simulations, described here, provides a new way to capture the structures of major-groove RNA triplexes that evade crystallographic characteriza-tion. This method yields excellent agreement between measured and computed WAXS profiles and allows for an atomically detailed visualization of these motifs. Using correlation maps, the relation-ship between well-defined features in the scattering profiles and real space characteristics of RNA molecules is defined, including the subtle conformational variations in the double-stranded RNA upon the incorporation of a third strand by base triples. This readily applicable approach has the potential to provide insight into interactions that stabilize RNA tertiary structure that enables function.