Development of Fluorine Nuclear Magnetic Resonance (NMR) Spectroscopy as a Versatile Probe of Structure and Chemical Environment in Proteins

有了这个奖项，化学系的生命过程计划的化学是资助教授安吉拉M。来自匹兹堡大学的Gronenborn和特拉华州大学的Tatyana Polenova。该研究项目涉及使用氟核磁共振（NMR），这是一种用于探测化学结构和几何形状的多功能化学分析工具。天然存在的元素的磁活性同位素，如氘（氢的一种形式），碳（C-13）和氮（N-15），最常在生物分子NMR中研究;然而，氟（F-19）是一种非常有吸引力和敏感的核，它提供了有关溶液和固体状态分子的丰富信息。这项研究计划的总体目标是建立氟-19 NMR光谱作为一种通用的方法来描述蛋白质的结构和几何形状。该项目涉及计算和实验方法的整合。更广泛的影响计划将科学培训与人文学科的研究相结合，努力使学生为向公众传播科学做好准备。此外，还有教育活动，涉及布鲁克学术研究人员和行业合作者的实验室之间的研究生交流计划。这些学生花2-3周的时间获得先进的实验生物物理化学，动手核磁共振光谱和仪器的补充培训。针对本科生和高中生的外联活动吸引了不同背景的学生进入科学、技术、工程和数学学科。该项目的具体目标是开发氟-19化学位移作为肽和蛋白质的几何结构，电子结构，化学反应性和动力学的探针。该项目将氟-19溶液和固态NMR参数与量子化学计算相结合。该研究利用了广泛的化学位移和氟-19位点的稀疏性，开发了溶液和固态NMR实验，用于绘制肽和蛋白质中的长程距离和相互作用位点。这项研究可能克服目前在计算生物化学系统的精确氟-19化学位移张量和基于氟的距离测量方面的挑战。鉴于氟的生物合成掺入到各种各样的特定和独特的网站的简单性，该方法使氟-19溶液和固态NMR应用于广泛的生物化学系统。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professors Angela M. Gronenborn from the University of Pittsburgh and Tatyana Polenova of the University of Delaware. The research project involves the use of fluorine nuclear magnetic spectroscopy (NMR), a versatile analytical tool in chemistry used for probing chemical structures and geometries. Naturally-occurring, magnetically-active isotopes of elements such as deuterium (a form of hydrogen), carbon (C-13) and nitrogen(N-15) are most commonly studied in biomolecular NMR; however, fluorine (F-19) is a very attractive and sensitive nucleus, which offers rich information about molecules in the solution and solid states. The overall goal of this research program is to establish fluorine-19 NMR spectroscopy as a versatile approach for describing the structure and geometry of proteins. The project involves an integration of computational and experimental approaches. The broader impact plans integrate scientific training with studies in the humanities in an effort to prepare students for communicating science to the public. In addition, there are educational activities that involve a graduate student exchange program between the laboratories of the academic researchers and industry collaborators at Bruker. These students spend 2-3 weeks acquiring complementary training in advanced experimental biophysical chemistry, hands-on NMR spectroscopy, and instrumentation. Outreach activities for undergraduates and high-school students attract students with diverse backgrounds into the science, technology, engineering and mathematics (STEM) disciplines. The specific objectives of this project are to develop fluorine-19 chemical shifts as a probe of geometry, electronic structure, chemical reactivity, and dynamics in peptides and proteins. The project integrates fluorine-19 solution and solid-state NMR parameters with quantum chemical calculations. The research exploits the vast range of chemical shifts and the sparsity of fluorine-19 sites, to develop solution and solid-state NMR experiments for mapping out long-range distances and interaction sites in peptides and proteins. The research may overcome the current challenges in the calculations of accurate fluorine-19 chemical shift tensors for biochemical systems and in fluorine-based distance measurements. Given the simplicity of biosynthetic incorporation of fluorine into a wide variety of specific and unique sites, the approaches enable fluorine-19 solution and solid-state NMR applications for a broad range of biochemical systems.