COMPUTATIONAL METHODS FOR STUDYING PROTEIN DYNAMICS BY ESR & NMR

通过 ESR 研究蛋白质动力学的计算方法

• 批准号: 7602606
• 负责人: Jack H Freed
• 金额: $ 0.62万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7602606
• 关键词: Classification; Communities; Complex; Computer Retrieval of Information on Scientific Projects Database; Computer software; Computing Methodologies; Coupled; Coupling; Data; Frequencies; Funding; Grant; Institution; Measures; Modeling; Motion; Muramidase; Output; Property; Protein Dynamics; Proteins; Rate; Relaxation; Research; Research Personnel; Resolution; Resources; Site; Source; Spin Labels; Structure; System; Temperature; United States National Institutes of Health; density; design; research study; theories

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have developed new models and software for analyzing the ESR and NMR data from protein 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. When coupled with the slowly relaxing local structure (SRLS) model, the multifrequency fit outputs the local dynamics and ordering of the tether connecting the probe to the protein as well as the overall tumbling rate of the whole protein complex. This approach has been applied to the study of the dynamic properties of T4 lysozyme spin labeled at several sites. A systematic analysis of the ESR spectra measured at different temperatures adds additional spectral resolution to the fitting parameters. Special focus has been placed on a comparison of the dynamics and ordering parameters amongst different sites. We have used these results to design new experiments, which allow an effective separation of different modes of motions. We are also upgrading the SRLS model to include three modes of motion, which is a better approximation of the complex protein dynamics. In the second part of this subproject, we have formulated the SRLS model within the context of NMR relaxation theory to analyze protein 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 dynamical analysis. This approach has been successfully applied to the dynamics analyses of a few protein systems. It is currently being extended to the calculation of the cross terms of NMR spectral density.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们开发了新的模型和软件，用于分析来自蛋白质系统的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。 当与缓慢放松的局部结构（SRL）模型结合使用时，多频拟合会输出将探针连接到蛋白质的系绳的局部动力学和排序，以及整个蛋白质复合物的整体翻滚速率。 这种方法已应用于在多个位点标记的T4溶菌酶自旋的动态特性的研究。 对在不同温度测得的ESR光谱的系统分析为拟合参数增加了额外的光谱分辨率。 特殊的重点已放在不同站点之间的动力学和订购参数的比较上。 我们已经使用这些结果来设计新的实验，从而有效地分离了不同的运动模式。 我们还将SRLS模型升级到包括三种运动模式，这是对复杂蛋白质动力学的更好近似。 在本次选项的第二部分中，我们在NMR弛豫理论的背景下制定了SRLS模型，以分析蛋白质动力学。 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分析的理解的重要一步。这种方法已成功应用于一些蛋白质系统的动力学分析。 目前，它正在扩展到NMR光谱密度的跨项的计算。