Comprehensive Error Analysis in NMR Relaxation for Accurate Assessment of Protein Dynamics

核磁共振弛豫中的综合误差分析可准确评估蛋白质动力学

• 批准号: 0814905
• 负责人: Rieko Ishima
• 金额: $ 41.39万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0814905&HistoricalAwards=false
• 关键词: Comprehensive; Error; Analysis; NMR; Relaxation

During the past two decades, advances in NMR and its related technologies have tremendously increased the sensitivity of NMR relaxation experiments. NMR-derived parameters now have sufficient sensitivity to allow comparison with parameters obtained by other methods, such as molecular dynamics simulations and thermodynamics experiments. However, for meaningful results to emerge and for reasonable comparison of NMR-derived dynamics with those obtained by other methods, accurate evaluation of uncertainties in the NMR-derived parameters is critical. The objective of this project is to provide a comprehensive assessment of the relaxation errors for a variety of experiments. Based on this assessment, uncertainty estimations will be incorporated into software packages to allow accurate extraction of protein dynamics. Such analyses will significantly impact the field and are crucial at the present time when NMR dynamics studies are increasingly used to interpret unique features in enzymatic mechanisms and other biological processes. The results of this research will be widely distributed via journal publications and websites, promoting their broad application in the NMR community and facilitating the development of new and existing analysis tools in the field. Removing impediments caused by improper error estimation, this work will allow the merging and integration of NMR results with those derived by other biophysical methods. Such seamless integration is important for future progress in Biophysics and Structural Biology. This project will also provide interdisciplinary training for students. An advanced NMR course comprising theory and experiments will be integrated into the Molecular Biophysics and Structural Biology Graduate Curriculum and increased opportunities for summer undergraduate research will be created. Also, science exposure in the local communities will be increased and Structural Biology will be brought to K-12 schools.

在过去的二十年中，NMR及其相关技术的进步极大地提高了NMR弛豫实验的灵敏度。 NMR衍生的参数现在有足够的灵敏度，允许与其他方法，如分子动力学模拟和热力学实验获得的参数进行比较。 然而，有意义的结果出现和合理的比较NMR衍生的动力学与其他方法获得的，NMR衍生参数的不确定性的准确评估是至关重要的。 这个项目的目的是提供一个全面的评估松弛误差的各种实验。 基于这一评估，将不确定性估计纳入软件包，以准确提取蛋白质动力学。 这种分析将显着影响该领域，是至关重要的，在目前的时候，NMR动力学研究越来越多地用于解释酶的机制和其他生物过程中的独特功能。 这项研究的结果将通过期刊出版物和网站广泛传播，促进其在NMR界的广泛应用，并促进该领域新的和现有的分析工具的开发。 这项工作消除了由错误估计造成的障碍，将允许合并和整合NMR结果与其他生物物理方法得出的结果。 这种无缝集成对于生物物理学和结构生物学的未来发展非常重要。 该项目还将为学生提供跨学科培训。 包括理论和实验的高级NMR课程将被整合到分子生物物理学和结构生物学研究生课程中， 将创造更多的夏季本科生研究机会。 此外，将增加当地社区的科学接触，并将结构生物学带到K-12学校。