INCISIVE PROBING OF NUCLEIC ACID CONFORMATIONAL HETEROGENEITY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 核酸复杂而崎岖的能量格局隐含着核酸的构象异质性，它控制着核酸的折叠和功能。此外，有越来越多的证据表明，瞬时中间产物以及蛋白质和结构RNA的最终折叠状态存在异质性。尽管核酸构象异质性具有重要的基础性意义，但由于缺乏合适的实验技术，这一问题一直没有得到很好的研究。一种新开发的基于Au-SAXS的X射线标尺提供了一组分子的距离概率分布。这一技术为研究大分子构象异质性提供了一种独特而有力的探针。我们建议研究模块化DNA和RNA结构的构象灵活性和异质性，包括A-道、凸起、单链和双链连接以及简单的功能RNA结构，如HIV TAR RNA。我们打算测量这些核酸结构中的构象分布和异质性，并将分布与核酸折叠和功能联系起来。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The conformational heterogeneity in nucleic acids is implied by the complex and rugged energy landscape of nucleic acids, which controls their folding and function. Moreover, there is increased evidence of heterogeneity in transient intermediates as well as the final folded state of proteins and structured RNAs. Despite the fundamental importance of conformational heterogeneity in nucleic acids, it has not been properly studied due to a lack of suitable experimental techniques. A newly developed Au-SAXS-based x-ray ruler provides the distance probability distribution of an ensemble of molecules. This technique provides a unique and powerful probe of macromolecular conformational heterogeneity. We propose to study the conformational flexibility and heterogeneity of modular DNA and RNA structures, including A-tract, bulges, single-stranded and double stranded junctions and simple functional RNA structure such as the HIV TAR RNA. We intend to measure the conformational distributions and heterogeneity in these nucleic acids structures and relate the distributions to nucleic acid folding and function.