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.
