Methodology for Rapid and Precise Measurement of NMR Parameters: Development and Application to Study Protein Structure and Folding

核磁共振波谱学在科学和工程中有着广泛的应用，但随着维数的增加，最小测量次数急剧增加，导致核磁共振波谱采样问题，从而阻碍了多维光谱信息的获取。此外，生物大分子的基于NMR的研究受到化学位移简并性的阻碍，部分原因是位移测量的精确度太低。 该项目的重点是开发快速核磁共振数据采集方法和数据采集方案，使人们能够更准确地测量核磁共振参数。具体地说，我们的目标是实现一个新的线的“同时循环”或“切片选择”的NMR实验（准）同时执行的射频脉冲相位的翻转角循环，并实施方案，以获取光谱的色散线分量，这阻碍了准确测量的位移。 这种新的方法将被应用于解决蛋白质结构的结构基因组学联盟的框架，以评估半自动数据分析和蛋白质折叠的影响。这种新的NMR方法将广泛影响科学界NMR数据采集的速度和准确性。 PI将建立一个门户网站，以确保有效传播结果。该项目非常适合教育年轻的研究人员在基于NMR的结构生物学，特别是在先进的方法开发和NMR的应用，研究蛋白质结构和折叠。 这项研究将考虑在化学和结构生物学系在州立大学在纽约在布法罗的年轻科学家的综合跨学科教学的具体需求进行。PI将提供物理化学和生命科学中使用NMR的本科生和研究生课程，他将继续支持本科生在实验室，暑期学校和大学的研究培训。 该项目由生物科学理事会分子和细胞生物科学部的分子生物物理学和数学和物理科学理事会化学部的实验物理化学计划共同支持。

NMR spectroscopy is widely used in science and engineering, but acquisition of multi-dimensional spectral information is hampered by the NMR sampling problem resulting from the steep increase of minimal measurement times with dimensionality. Furthermore, NMR-based studies of biological macromolecules are impeded by chemical shift degeneracy, in part resulting from comparably low accuracy of shift measurements. The focus of this project is on the development of methodology for rapid NMR data acquisition and data acquisition schemes enabling one to measure NMR parameters more accurately. Specifically, the objective is to implement a new line of "simultaneously cycled" or "slice selected" NMR experiments to (quasi) simultaneously execute radio-frequency pulse phase of flip-angle cycling, and to implement schemes to acquire spectra devoid of dispersive line components, which impede accurate measurement of shifts. This new methodology will be applied to solve protein structures in the framework of structural genomics consortia in order to assess impact on semi-automated data analysis and protein folding. This new NMR methodology will broadly impact on the speed and accuracy of NMR data acquisition in the scientific community. The PI will set up a web portal to ensure efficient dissemination of results. This project is well suited to educate young researchers in NMR-based structural biology, in particular in advanced methodology development and application of NMR to study protein structure and folding. The research will be conducted considering the specific demands for comprehensive interdisciplinary teaching of young scientists at the Departments of Chemistry and Structural Biology at the State University at New York at Buffalo. The PI will offer undergraduate and graduate level courses in Physical Chemistry and on the use of NMR in life sciences, and he will continue to support research training of undergraduate students in the laboratory, in summer schools and in colleges. This project is jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences and the Experimental Physical Chemistry Program in the Division of Chemistry in the Mathematical and Physical Sciences Directorate.