Exploring the Dynamic Structures of Nucleic Acids

探索核酸的动态结构

• 批准号: 10330054
• 负责人: LOIS POLLACK
• 金额: $ 44万
• 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 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10330054
• 关键词: Biological; Biology; Coupled; DNA; Disease; Drug Targeting; Elements; Gene Expression; Genes; Genetic Translation; Ions; Ligands; Malignant Neoplasms; Measurement; Modeling; Molecular Conformation; Motivation; Nucleic Acids; Pharmaceutical Preparations; Proteins; RNA; Resolution; Role; Signal Transduction; Structure; Techniques; Therapeutic Intervention; Vaccines; Variant; base; computerized tools; flexibility; insight; molecular scale; new therapeutic target; nucleic acid structure; programs; protein complex; targeted treatment

The increasing recognition of RNA’s importance provides strong motivation for understanding how its dynamic structures contribute to biology at the molecular scale. Much of RNA’s versatility is derived from its intrinsic conformational flexibility and capacity to interact with a broad range of cellular partners. Assessment of RNA’s structures is challenged by the variations that supports these multiple roles. This program supports the continued application of tightly coupled experimental and computational tools to characterize ensembles of RNA structures. Recent advances enhance the resolution or interpretation of solution-based measurements, revealing subtle but important changes in rigid elements, like duplexes, or the full range of structures assumed by highly flexible unpaired strands. This project now extends studies of RNA from isolated motifs to biologically functional elements and aims to resolve their atomically detailed workings. A distinct focus is on the structural variation of single-stranded motifs. The capture or release of these highly flexible regions is a potent signal exploited in regulating the translation of mRNAs into proteins, via interactions with ions, small ligands or RNA motifs such as duplexes or loops in helix-junction-helix motifs. Because of their importance in controlling gene expression, these motifs offer new targets for therapeutic intervention or strategies for stabilizing existing RNA-based drugs or vaccines. Finally, this project will continue successful efforts to characterize the interaction of flexible nucleic acid motifs with proteins, laying the groundwork for understanding how large nucleic acid-protein complexes function.

对RNA重要性的越来越多的认识为理解的强大动力提供了强大的动力 其动态结构如何在分子尺度上有助于生物学。 RNA的大部分多功能性 源自其内在的会议灵活性和与广泛范围相互作用的能力 蜂窝伙伴。支持RNA结构的评估受到支持的变化的挑战 这些多个角色。该程序支持连续耦合的继续应用 实验和计算工具以表征RNA结构的合奏。最近的 进步增强了基于解决方案的测量的分辨率或解释，揭示了 刚性元素（例如复式）或整个结构的细微但重要的变化 由高度柔韧的未配对链假设。现在，该项目扩展了对RNA的研究 孤立的生物学功能元素的基序，旨在解决其原子详细的 工作。独特的重点是单链基序的结构变化。捕获或 这些高度灵活区域的释放是调节翻译的潜在信号 通过与离子，小配体或RNA图案（例如双链体或 螺旋结螺旋图案中的循环。由于它们在控制基因表达方面的重要性，所以 这些图案为治疗干预或稳定现有的策略提供了新的目标 基于RNA的药物或疫苗。最后，该项目将继续成功地努力来表征 柔性核酸基序与蛋白质的相互作用，为 了解大核酸蛋白质复合物的功能。