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、相互作用和功能是非常重要的。该项目的总体目标是开发新的方法，通过将核磁共振光谱与先进的计算机模拟相结合来全面描述蛋白质的复杂动力学，并将这些方法应用于具有生物重要性的分子系统。为了实现这些目标，所有氨基酸侧链的核磁共振化学位移将利用数据库信息和分子动力学轨迹在微秒范围内根据它们的结构和环境被定量地参数化。它们将允许对蛋白质整体的质量进行严格评估，例如由长分子动力学轨迹产生的蛋白质。这些工具将与实验核磁共振一起用于提高低分辨蛋白质结构的准确性，并用于表征变构调节和高塑性配体结合。该项目将生产新的算法、网络服务器和软件，以日益准确和现实地描述蛋白质在其自然环境中的特征。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。这些工具将可用于结构生物学、生物物理学和生物分子核磁共振领域。该项目将为佛罗里达州立大学(FSU)化学和生物化学系、FSU分子生物物理研究所和国家强磁场实验室(NHMFL)的本科生、研究生和博士后提供跨学科培训和研究机会，其中大量学生来自人口统计数据不足的群体。研究方法和成果将被纳入生物物理学和生物分子光谱学的本科生和研究生课程。这项研究的精选范例将在NHMFL的年度开放参观活动上展示，该活动吸引了北佛罗里达州及其附近地区广泛的人口，有助于提高公众的科学素养。白求恩-库克曼大学(BCU)的一名助理教授将获得每年夏天在PI的实验室度过的空间和资源，这将计入他的专业发展活动。BCU是佛罗里达州的一所历史上的黑人学院。他将带着BCU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.