Nucleic acid interactions with partners: ions and proteins

核酸对生命至关重要，但详细了解这些多样而复杂的 大分子功能仍然遥不可及。DNA储存并传播遗传信息 从高度结构化的染色质中。在过去的三十年里，意想不到的，往往令人惊讶的生物学 已经发现了RNA的作用。RNA在细胞中的活跃作用包括调节基因， 防止感染。涉及RNA的发现的快速步伐远远超过了目前的知识， 这些非凡的分子是如何运作的 核酸（NA）的许多最重要的作用依赖于折叠成紧凑的结构，尽管大的 主链的负电荷，由于电荷之间的排斥力而有利于延伸结构。 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。RNA 折叠成功能性结构是由于与带正电荷的配偶体相互作用。这个目标 该计划旨在了解生物学上重要的合作伙伴如何相互作用，并影响/控制的结构， DNA和RNA。 关于DNA和RNA结构的双链双链体区域，我们知道得很多。所以我们的 对DNA的研究将集中在蛋白质伴侣如何将长双链体压缩（释放）到（从）NCP中。在 相比之下，对于RNA，这是必要的单链，更少的信息是关于灵活的 连接短的刚性双链体并使折叠、传感或蛋白质结合成为可能的连接器。创新 实验工具将被应用于测量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 独立折叠的RNA基序，到大的蛋白质-DNA复合物。 与成熟的研究人员进行多次合作，通常基于多年的NIH共享资金， 使这个计划的广度。拟议的合作研究包括：优化力场， 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，测试和完善NA元素的溶液和离子环境的隐式溶剂模型， 最后是以生物学为导向的研究，重点是蛋白质在染色质动态运动中的作用。

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.