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.

有了这个奖项，博士。爱德华·尼科诺维奇（Edward Nikonowicz）（赖斯大学）和张张（M. D. Anderson Cancer Center）将识别和表征与独特的RNA结构基序有选择地结合的小分子。该奖项是通过化学过程的化学过程（CLP）计划，分子和细胞生物科学划分的遗传机制集群以及NSF的计算和数据支持科学与工程计划的。核糖酸（RNA）在生物学中的核心作用长期以来已经识别出来，但是大量未转化为蛋白质的“非编码” RNA分子，这些RNA的各种功能仅在过去十年中才亮起。该项目的目的是确定具有高选择性和亲和力与非编码RNA分子中异常结构的小元素结合的化合物的集合。这些化合物可以用作生物技术和生化研究以及医学应用的新工具。除了通过研究生的研究来支持培训外，该项目还将支持对现代化学，生物物理和计算工具的高中和本科生的培训，以解决RNA和化学生物学的基本问题。学生在当地的科学会议上介绍他们的工作，使他们接触科学界的机会，并有机会将其结果传达给科学识字但广泛的受众群体。编码RNA（NC-RNA），包括RRNA，RIBOSWITCHES和MICRRERNAS，通常都具有各种非企业的建筑，其中包括各种非核类特征对核心的结构和构造功能。因此，详细的结构为解释功能和机械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光谱法将用于定义一组经常发生的非典型RNA元素访问的构象空间的广度。将开发一种集成NMR定义的结构信息和虚拟化学文库的计算机筛选的计算工作流程，以鉴定有选择地与特定非典型元素结合的化学化合物。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光谱和X射线晶体学）进行表征。