Collaborative Research:Recognition of RNA Structure Motifs Using Small Molecules

有了这个奖项，dr。Edward Nikonowicz（莱斯大学）和Shuxing Zhang（安德森癌症中心）将鉴定和表征选择性结合独特RNA结构基元的小分子。该奖项是通过美国国家科学基金会化学分部的生命过程化学（CLP）项目、分子和细胞生物科学部的遗传机制集群以及计算和数据支持科学与工程（CDS&amp；E）项目获得的。核糖核酸（RNA）在生物学中的核心作用早已被认识到，但大量的“非编码”RNA分子，它们不能翻译成蛋白质，以及这些RNA的多种功能直到最近十年才被发现。该项目的目标是鉴定一组具有高选择性和亲和力的化合物，这些化合物与非编码RNA分子中发现的不寻常结构的小元素结合。这些化合物可作为生物技术和生物化学研究的新工具以及在医学上的应用。除了通过研究生的研究支持培训外，该项目还将支持高中和本科生使用现代化学、生物物理和计算工具来解决RNA和化学生物学中的基本问题的培训。学生们在当地的科学会议上展示他们的工作，使他们有机会接触科学界，并有机会将他们的成果传达给具有科学素养的广大受众。非编码rna (nc-RNA)，包括rrna、核糖开关和前microrna，通常具有包括各种非规范特征的结构，这些特征对分子的结构和功能很重要。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。结合特定RNA结构基序的小分子可以成为探测RNA构象和折叠的有力工具，并有助于研究体外和体内特定RNA的活性。核磁共振波谱将用于定义由一组频繁出现的非规范RNA元件访问的构象空间的宽度。将开发一个集成核磁共振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进行表征，包括核磁共振波谱和x射线晶体学。

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.