Collaborative Research:Recognition of RNA Structure Motifs Using Small Molecules

合作研究：利用小分子识别RNA结构基序

基本信息

批准号：
1412864
负责人：
Edward Nikonowicz
金额：
$ 31万
依托单位：
William Marsh Rice University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1412864&HistoricalAwards=false
关键词：
Collaborative Research Recognition RNA Structure

项目摘要

With this award, Drs. Edward Nikonowicz (Rice University) and Shuxing Zhang (M. D. Anderson Cancer Center) will identify and characterize small molecules that selectively bind to unique RNA structure motifs. This award is being made through the Chemistry of Life Processes (CLP) Program of the Chemistry Division, the Genetic Mechanisms Cluster of the Division of Molecular and Cellular Biosciences, and the Computational and Data-Enabled Science and Engineering (CDS&E) Program at NSF. The central role of ribonucleic acids (RNAs) in biology has long been recognized, but the large number of "non-coding" RNA molecules, which are not translated into a protein, and the diverse functions of these RNAs have only come to light in the last decade. The goal of this project is to identify a collection of chemical compounds that bind with high selectivity and affinity to small elements of unusual structure found in non-coding RNA molecules. These compounds could be used as new tools for biotechnological and biochemical research and for applications in medicine. In addition to supporting the training through research of graduate students, this project will support training of high-school and undergraduate students in the use of modern chemical, biophysical, and computational tools to address fundamental problems in RNA and chemical biology. Students present their work at local scientific meetings, giving them exposure to the scientific community and the opportunity to communicate their results to a scientifically literate, yet broad audience.Non-coding RNAs (nc-RNA), including rRNAs, riboswitches, and pre-microRNAs, often have an architecture that includes a variety of non-canonical features important for the molecules' structures and function. Therefore, the detailed structure provides an important backdrop to interpret functional and mechanistic studies. Small molecules that bind to specific RNA structure motifs can become powerful tools for probing RNA conformation and folding and to facilitate the study of specific RNA activities in vitro and in vivo. NMR spectroscopy will be used to define the breadth of conformational space accessed by a set of frequently occurring non-canonical RNA elements. A computational workflow that integrates the NMR-defined structure information and the in silico screening of virtual chemical libraries will be developed to identify chemical compounds that selectively bind to specific non-canonical elements. The interactions of these small molecules with RNAs will be characterized using biophysical and high-resolution structure methods including NMR spectroscopy and X-ray crystallography.

凭借此奖项，博士。 Edward Nikonowicz（莱斯大学）和 Shuxing Zhu（MD 安德森癌症中心）将鉴定和表征选择性结合独特 RNA 结构基序的小分子。该奖项是通过化学部的生命过程化学 (CLP) 项目、分子和细胞生物科学部的遗传机制集群以及 NSF 的计算和数据支持的科学与工程 (CDS&E) 项目颁发的。核糖核酸 (RNA) 在生物学中的核心作用早已被人们所认识，但大量的“非编码”RNA 分子（它们不翻译成蛋白质）以及这些 RNA 的多种功能直到现在才被人们所认识。过去十年。该项目的目标是鉴定一系列化合物，这些化合物能够以高选择性和亲和力与非编码 RNA 分子中发现的异常结构的小元件结合。这些化合物可用作生物技术和生物化学研究以及医学应用的新工具。除了支持研究生研究培训外，该项目还将支持高中生和本科生使用现代化学、生物物理和计算工具解决 RNA 和化学生物学基本问题的培训。学生在当地的科学会议上展示他们的工作，让他们接触科学界，并有机会向具有科学素养的广泛受众传达他们的成果。非编码 RNA (nc-RNA)，包括 rRNA、核糖开关和预RNA microRNA 通常具有包含对分子结构和功能很重要的各种非规范特征的架构。因此，详细的结构为解释功能和机制研究提供了重要的背景。与特定 RNA 结构基序结合的小分子可以成为探测 RNA 构象和折叠的强大工具，并促进体外和体内特定 RNA 活性的研究。 NMR 波谱将用于定义一组频繁出现的非规范 RNA 元件所访问的构象空间的宽度。将开发集成 NMR 定义的结构信息和虚拟化学库的计算机筛选的计算工作流程，以识别选择性结合特定非规范元素的化合物。这些小分子与 RNA 的相互作用将使用生物物理和高分辨率结构方法（包括 NMR 光谱学和 X 射线晶体学）进行表征。