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

在过去的二十年里，核磁共振及其相关技术的进步极大地提高了核磁共振弛豫实验的灵敏度。核磁共振得到的参数现在具有足够的灵敏度，可以与其他方法获得的参数进行比较，例如分子动力学模拟和热力学实验。然而，要想得到有意义的结果，并将核磁共振衍生的动力学与其他方法得到的结果进行合理的比较，准确评估核磁共振衍生参数中的不确定性是至关重要的。这个项目的目的是为各种实验提供一个全面的松弛误差评估。在此评估的基础上，不确定度估计将被合并到软件包中，以便准确提取蛋白质动力学。这种分析将对该领域产生重大影响，在核磁共振动力学研究越来越多地被用于解释酶机制和其他生物过程中的独特特征的情况下，这一分析是至关重要的。这项研究的结果将通过期刊出版物和网站广泛分发，促进它们在核磁共振社区的广泛应用，并促进该领域新的和现有分析工具的开发。排除错误估计造成的障碍，这项工作将允许将核磁共振结果与其他生物物理方法得出的结果合并和集成。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核磁共振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，并将创造更多的暑期本科生研究机会。此外，还将增加当地社区的科学曝光率，并将结构生物学带到K-12学校。

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.