PROBING OF NUCLEIC ACID CONFORMATIONAL HETEROGENEITY: STARTING WITH DNA BULGES

核酸构象异质性的探测：从 DNA 凸出开始

• 批准号: 8170235
• 负责人: Xuan-Zheng Peter Shi
• 金额: $ 0.1万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170235
• 关键词: Computer Retrieval of Information on Scientific Projects Database; DNA; Funding; Gold; Grant; Heterogeneity; Institution; Investigation; Label; Length; Measures; Molecular; Nucleic Acid Probes; Nucleic Acids; Nucleotides; Probability; Property; RNA; Research; Research Personnel; Resources; Series; Solutions; Source; Staging; Techniques; United States National Institutes of Health; base; flexibility; nanocrystal

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Using small-angle x-ray scattering interference between gold nanocrystal labels, Mathew-Fenn et al. measured the end-to-end length for a series of DNA double helices in solution. This newly developed Au-SAXS-based x-ray ruler determines the distance probability distribution of an ensemble of molecules, providing a unique and powerful probe of macromolecular conformational heterogeneity. To establish the ability of this x-ray ruler technique to measure the distance distribution of molecular ensembles, we propose to study the conformational flexibility and heterogeneity in DNA helices with bulged nucleotides. A-bulges have been shown to bend DNA, giving a good starting point for these studies, but the degree of underlying conformational heterogeneity is unknown. We will compare the effect of A and U bulges of length 1-5 on DNA bending and heterogeneity. These studies would set the stage for incisive investigation of RNA molecules and their structural and dynamic properties. Toward this end, we will use the initial results in a full proposal for the systematic study of nucleic acid conformational heterogeneity, including DNA A-tract, and RNA bulges.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 Mathew-Fenn 等人利用金纳米晶体标记之间的小角度 X 射线散射干扰。测量了溶液中一系列 DNA 双螺旋的端到端长度。这种新开发的基于 Au-SAXS 的 X 射线标尺可确定分子集合的距离概率分布，为大分子构象异质性提供独特而强大的探针。为了建立这种 X 射线标尺技术测量分子集合体距离分布的能力，我们建议研究具有凸出核苷酸的 DNA 螺旋的构象灵活性和异质性。 A-凸起已被证明可以弯曲 DNA，为这些研究提供了一个良好的起点，但潜在的构象异质性程度尚不清楚。我们将比较长度为 1-5 的 A 和 U 凸起对 DNA 弯曲和异质性的影响。这些研究将为 RNA 分子及其结构和动态特性的深入研究奠定基础。为此，我们将在完整的提案中使用初步结果来系统研究核酸构象异质性，包括DNA A-tract和RNA凸起。