COMPUTATIONAL METHODS FOR STUDYING PROTEIN AND DNA DYNAMICS BY ESR & NMR

通过 ESR 研究蛋白质和 DNA 动力学的计算方法

• 批准号: 8364005
• 负责人: ZHICHUN LIANG
• 金额: $ 1.63万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364005
• 关键词: Communities; Complex; Computer software; Computing Methodologies; Coupled; Coupling; DNA; Data; Diffusion; Frequencies; Funding; Grant; Maryland; Modeling; Motion; Muramidase; National Center for Research Resources; Output; Principal Investigator; Property; Protein Dynamics; Proteins; Relaxation; Research; Research Infrastructure; Resolution; Resources; Site; Solvents; Source; Spin Labels; Structure; System; Technology; Ubiquitin; United States National Institutes of Health; Universities; conformer; cost; macromolecule; mutant; programs; theories

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have developed new models and software for analyzing the ESR and NMR data from macromolecules such as protein and DNA systems. In the ESR context, the new software allows a simultaneous fit of ESR spectra at different frequencies to enhance the spectral resolution to the various fitting parameters. It also allows for dynamic exchanges between conformers. When coupled with the slowly relaxing local structure (SRLS) model, the multi frequency fit outputs the local dynamics and ordering of the tether connecting the spin label to the macromolecule as well as the overall tumbling rate of the whole macromolecule complex. This approach has been applied to the study of the dynamic properties of T4 lysozyme spin labeled at several mutant sites. Currently we are conducting a more comprehensive study of T4 lysozyme dynamics at more mutant sites and more frequencies in different solvents. We are adding new features to our fitting programs. These features include (1) an asymmetric diffusion tensor for the internal motion of the spin label and (2) an internal diffusion tilt with all three Euler angles. In the second part of this subproject, we have formulated the SRLS model within the context of NMR relaxation theory to analyze macromolecule dynamics. An important assumption of the widely used model free (MF) theory in the protein NMR community is the decoupling between the two modes of motions. The dynamical coupling of the overall protein tumbling and the local motion is an important step forward towards our understanding of the protein dynamics. This approach has been successfully applied to the dynamics analyses of a few protein systems, and will be used in a NMR study by Dr David Fushman, University of Maryland, to analyze the overall and inter-domain motions in dual-domain (di-ubiquitin) system.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们开发了新的模型和软件，用于分析来自大分子（例如蛋白质和DNA系统）的ESR和NMR数据。在ESR上下文中，新软件允许在不同频率上同时拟合ESR光谱，以增强光谱分辨率到各种拟合参数。它还允许在构象异构体之间进行动态交流。当与缓慢放松的局部结构（SRL）模型结合使用时，多频率拟合会输出局部动力学和连接旋转标签与大分子的束缚和排序，以及整个大分子复合物的整体翻滚速率。 这种方法已应用于在几个突变位点标记的T4溶菌酶自旋的动态特性的研究。目前，我们正在对更突变的位点上的T4溶菌酶动力学进行更全面的研究，并在不同的溶剂中进行更多的频率。我们正在为拟合程序添加新功能。这些特征包括（1）自旋标记的内运动的不对称扩散张量，以及（2）具有所有三个Euler角的内部扩散倾斜。在本次审计的第二部分中，我们在NMR弛豫理论的背景下制定了SRLS模型，以分析大分子动力学。 蛋白质NMR社区中广泛使用模型（MF）理论的重要假设是两种运动模式之间的脱钩。 整体蛋白质翻滚和局部运动的动态耦合是我们对蛋白质动力学理解的重要一步。这种方法已成功地应用于一些蛋白质系统的动力学分析，并将在马里兰州大学的David Fushman博士的NMR研究中使用，以分析双域（Di-ubiquitin）系统中的整体和域间运动。