Nucleic acid interactions with partners: ions and proteins

核酸对生命来说是必不可少的，但对这些多样性和复杂性的详细了解 大分子的功能仍然遥不可及。DNA存储和传播遗传信息 从高度结构化的染色质内部。在过去的三十年里，出乎意料且经常令人惊讶的生物 人们已经发现了RNA的作用。RNA在细胞中的活跃作用范围从调节基因到 防止感染。有关RNA的快速发现速度远远超过了目前对 这些非凡的分子是如何发挥作用的。 核酸的许多最重要的作用依赖于折叠到紧凑的结构，尽管有很大的 主干的负电荷，由于电荷之间的排斥力，有利于延伸的结构。 在染色质中，DNA被蛋白质包装成称为核小体核心颗粒(NCP)的小单位。核糖核酸 折叠成功能结构是与带正电的伴侣相互作用的结果。这样做的目的是 该计划旨在了解具有生物本质的伴侣如何与其相互作用并影响/控制其结构。 DNA和RNA。 关于DNA和RNA结构的双链双链区域，我们知道得很多。因此，我们的 对DNA的研究将集中在蛋白质伴侣如何将长双链压缩(释放)成NCP。在……里面 相比之下，对于基本的单链RNA来说，关于柔性的信息要少得多 连接短而硬的双链并实现折叠、感应或蛋白质结合的连接器。创新型 实验工具将用于测量NA构象以及对两者构象的影响 蛋白质和离子伴侣。感兴趣的系统范围从短的单链区域到 独立地折叠RNA基序，形成大的蛋白质-DNA复合体。 与知名调查人员的多次合作，通常建立在NIH多年共享资金的基础上， 启用此计划的广度。建议的协作研究包括：优化力场以描述 高度灵活的NA结构，RNA折叠或RNA-蛋白质的全原子分子动力学(MD)模拟 相互作用，测试和改进NA元素的溶液和离子环境的隐含溶剂模型， 最后是侧重于蛋白质在染色质动态运动中的作用的生物学研究。

Nucleic acids are essential to life, yet a detailed understanding of how these diverse and complex macromolecules function remains beyond reach. DNA stores and enables propagation of genetic information from within highly structured chromatin. In the last thirty years, unanticipated and often surprising biological roles have been discovered for RNA. RNA's active roles in the cell range from regulating genes through protecting against infection. The rapid pace of discoveries involving RNA far exceeds current knowledge of how these remarkable molecules function. Many of the most important roles of nucleic acids (NAs) rely on folding to compact structures, despite the large negative charge of the backbone, which favors extended structures due to repulsive forces between charges. In chromatin, DNA is packaged by proteins into small units known as nucleosome core particles (NCPs). RNA folding to functional structures results from interactions with positively charged partners. The goal of this program is to understand how biologically essential partners interact with and affect/control the structures of DNA and RNA. Much is known about the double stranded duplex regions of both DNA and RNA structures. Therefore, our studies of DNA will focus on how protein partners compact (release) long duplexes into (from) NCPs. In contrast, for RNA, which is essential single stranded, much less information is available about the flexible connectors that link short, rigid duplexes and enable folding, sensing or protein binding. Innovative experimental tools will be applied to measure NA conformation as well as the effect on conformation of both protein and ionic partners. Systems of interest range from short, single stranded regions, through independently folding RNA motifs, to large protein-DNA complexes. Multiple collaborations with well-established investigators, often grounded in years of shared NIH funding, enable the breadth of this program. Proposed collaborative studies include: optimizing force fields to describe highly flexible NA structures, all atom molecular dynamics (MD) simulations of RNA folding or RNA-protein interactions, testing and refining implicit solvent models of the solution and ion environment of NA elements, and finally biologically oriented studies that focus on the role of proteins in dynamic motions of chromatin.