Nucleic acid interactions with partners: ions and proteins

核酸与伙伴的相互作用：离子和蛋白质

• 批准号: 10215554
• 负责人: LOIS POLLACK
• 金额: $ 40.42万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215554
• 关键词: Affect; Binding; Binding Proteins; Biological; Cells; Charge; Chromatin; Chromatin Structure; Collaborations; Complex; DNA; DNA Structure; Disease; Drug Targeting; Elements; Environment; Funding; Genes; Goals; Infection; Ions; Knowledge; Life; Link; Malignant Neoplasms; Measurement; Measures; Modeling; Molecular Conformation; Motion; Nucleic Acid Conformation; Nucleic Acids; Nucleosome Core Particle; Proteins; RNA; RNA Folding; RNA-Protein Interaction; Research Personnel; Role; Solvents; Structure; System; Techniques; Testing; United States National Institutes of Health; Vertebral column; flexibility; genetic information; innovation; insight; interest; macromolecule; molecular dynamics; nucleic acid structure; programs; targeted treatment; tool

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.

核酸对生命至关重要，但要详细了解这些多样化和复杂的物质是如何形成的 大分子功能仍然遥不可及。 DNA 存储并促进遗传信息的传播 来自高度结构化的染色质内部。在过去的三十年里，意想不到的、常常令人惊讶的生物 RNA 的作用已被发现。 RNA 在细胞中的积极作用包括调节基因 防止感染。涉及 RNA 的发现速度之快远远超过了目前的知识 这些非凡的分子如何发挥作用。 核酸 (NA) 的许多最重要的作用都依赖于折叠来压缩结构，尽管核酸的体积很大。 主链的负电荷，由于电荷之间的排斥力而有利于扩展结构。 在染色质中，DNA 被蛋白质包装成称为核小体核心颗粒 (NCP) 的小单元。核糖核酸 折叠成功能结构是与带正电的伙伴相互作用的结果。此举的目标 计划的目的是了解生物重要伙伴如何相互作用并影响/控制结构 DNA 和 RNA。 关于 DNA 和 RNA 结构的双链双链体区域，人们已经了解很多。因此，我们的 DNA 的研究将集中于蛋白质伴侣如何将长双链体压缩（释放）到 NCP 中。在 相比之下，对于必需的单链RNA而言，关于柔性RNA的信息要少得多。 连接短、刚性双链体并实现折叠、传感或蛋白质结合的连接器。创新的 实验工具将用于测量 NA 构象以及对两者构象的影响 蛋白质和离子伙伴。感兴趣的系统范围从短的单链区域，到 独立折叠RNA基序，形成大的蛋白质-DNA复合物。 与知名研究人员的多次合作，通常基于多年的 NIH 共同资助， 扩大该计划的广度。拟议的合作研究包括： 优化力场来描述 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，测试和完善NA元素溶液和离子环境的隐式溶剂模型， 最后是生物学导向的研究，重点关注蛋白质在染色质动态运动中的作用。