Dynamics and Function of Proteins by NMR and Computation

在原子水平上关于蛋白质结构和动力学的详细信息对于理解蛋白质的稳定性、相互作用和功能至关重要。该项目的总体目标是开发新方法，通过将NMR光谱与先进的计算机模拟相结合，全面描述蛋白质的复杂动力学，并将这些方法应用于生物学上重要的分子系统。为了实现这些目标，所有氨基酸侧链的NMR化学位移将使用数据库信息和分子动力学轨迹在微秒范围内对其结构和环境进行定量参数化。它们将允许严格评估蛋白质集合的质量，例如由长分子动力学轨迹产生的蛋白质集合。这些工具与实验NMR一起将被应用于低分辨率蛋白质结构的准确性的提高和变构调节和高可塑性配体结合的表征。该项目将产生新的算法，网络服务器和软件，用于在天然环境中越来越准确和逼真地表征蛋白质。核磁共振波谱与高性能计算的结合将适用于广泛的生物分子体系。这些工具将提供给结构生物学，生物物理学和生物分子NMR社区。该项目将提供跨学科的培训和研究的机会，本科生在前苏联的“荣誉在主要程序”，研究生，并在化学和生物化学系在佛罗里达州立大学（FSU），在分子生物物理研究所在前苏联，并在国家高磁场实验室（NHMFL）的博士后，从人口统计学上代表性不足的群体的学生人数众多。研究方法和结果将纳入本科生和研究生课程的生物物理学和生物分子光谱学。这项研究的选定例子将在NHMFL的年度开放日上展示，该开放日吸引了北佛罗里达及其附近地区的广泛人口，有助于提高公众的科学素养。位于佛罗里达的一所历史悠久的黑人大学白求恩-库克曼大学（BCU）的一位助理教授将获得空间和资源，每年夏天都可以在PI的实验室度过，这将有助于他的专业发展活动。他将带着北京大学的少数民族本科生一起开展核磁共振参数计算和分析的研究。

Detailed information about protein structure and dynamics at an atomic level is of fundamental importance for understanding protein stability, interactions, and function. The overall goals of this project are the development of new methods for a comprehensive description of complex dynamics of proteins by combining NMR spectroscopy with advanced computer simulations and the application of these methods to biologically important molecular systems. To achieve these objectives, NMR chemical shifts of all amino acid side-chains will be quantitatively parametrized in terms of their structure and environment using databank information and molecular dynamics trajectories into the microsecond range. They will permit the rigorous assessment of the quality of protein ensembles such as ones generated by long molecular dynamics trajectories. These tools together with experimental NMR will be applied for the improvement of the accuracy of low-resolution protein structures and for the characterization of allosteric regulation and high-plasticity ligand binding. The project will produce new algorithms, web servers, and software for the increasingly accurate and realistic characterization of proteins in their native environment. The combination of NMR spectrosccopy with high-performance computation will be applicable to a wide range of biomolecular systems. These tools will be made available to the structural biology, biophysics, and biomolecular NMR communities. This project will provide interdisciplinary training and research opportunities for undergraduate students in FSU's "Honors in the Major program", graduate students, and postdocs at the Department of Chemistry and Biochemistry at Florida State University (FSU), at the Institute of Molecular Biophysics at FSU, and at the National High Magnetic Field Laboratory (NHMFL), with significant numbers of students from demographically underrepresented groups. Research methods and results will be incorporated into undergraduate and graduate courses on biophysics and biomolecular spectroscopy. Selected examples of this research will be presented at the annual Open House at the NHMFL, which attracts a broad cross section of the population of North Florida and its vicinity, helping to increase scientific literacy of the public. An assistant professor at Bethune-Cookman University (BCU), a historically black college in Florida, will be provided space and resources to spend each summer in the PI's lab, which will count toward his professional development activities. He will bring minority undergraduate students with him from BCU to carry out research on NMR parameter calculations and analysis.