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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们开发了新的模型和软件，用于分析蛋白质和 DNA 系统等大分子的 ESR 和 NMR 数据。在 ESR 背景下，新软件允许同时拟合不同频率的 ESR 光谱，以增强各种拟合参数的光谱分辨率。它还允许构象异构体之间进行动态交换。当与缓慢松弛局部结构（SRLS）模型相结合时，多频率拟合输出连接自旋标签与大分子的系链的局部动力学和排序以及整个大分子复合物的整体翻滚速率。 该方法已应用于研究几个突变位点自旋标记的 T4 溶菌酶的动态特性。目前，我们正在对不同溶剂中更多突变位点和更多频率的 T4 溶菌酶动力学进行更全面的研究。我们正在为我们的验配程序添加新功能。这些特征包括（1）用于自旋标签内部运动的不对称扩散张量和（2）具有所有三个欧拉角的内部扩散倾斜。在该子项目的第二部分中，我们在 NMR 弛豫理论的背景下制定了 SRLS 模型来分析大分子动力学。 蛋白质 NMR 界广泛使用的无模型 (MF) 理论的一个重要假设是两种运动模式之间的解耦。 整体蛋白质翻滚和局部运动的动态耦合是我们理解蛋白质动力学的重要一步。该方法已成功应用于一些蛋白质系统的动力学分析，并将用于马里兰大学 David Fushman 博士的 NMR 研究，以分析双域（双泛素）中的整体和域间运动。 ） 系统。