Equipment Supplement: Analysis tools for quantifying protein conformational landscapes using DEER spectroscopy

项目总结/摘要 本项目开发了DEER（双电子-电子）的新的计算分析和建模方法 共振）光谱学。DEER是一种用于定量蛋白质构象的生物结构技术， 纳米尺度上的景观和蛋白质运动。蛋白质运动对于许多关键分子 是人类生命和疾病的基础。因此，DEER提供了重要的见解， 药物开发所需的知识基础。结合X射线晶体学、NMR和 cryo-EM，DEER是一套互补的综合实验生物结构工具的一部分。特别 对膜蛋白的研究很重要。该领域的一个主要障碍是缺乏综合分析工具 for biomedical生物医学researchers研究人员.本项目通过以下方式解决这一问题：（a）开发基于贝叶斯统计的工具 用于对实验DEER数据进行严格和可重复的分析，提供全面的方法， DEER数据中的不确定性量化（误差条），以及（B）创建高级计算工具以利用 DEER数据在基于原子分辨率系综模型的蛋白质结构精化中的应用。总体看 该项目的目标是显著加快DEER数据分析、解释和建模的工作流程 并增加其严谨性、可重复性和可访问性。这将使研究的结构和动力学 更大、更复杂的蛋白质和蛋白质组装体，在生物医学领域越来越重要。 research.

PROJECT SUMMARY/ABSTRACT This project develops new computational analysis and modeling methods for DEER (double electron-electron resonance) spectroscopy. DEER is a biostructural technique for the quantification of protein conformational landscapes and protein motions on the nanometer scale. Protein motions are crucial for many key molecular processes at the basis of human life and disease. Therefore, DEER provides important insights that contribute to the knowledge base necessary for drug development. In combination with X-ray crystallography, NMR and cryo-EM, DEER is part of a complementary set of integrative experimental biostructural tools. It is especially important for the study of membrane proteins. A major barrier in the field is the lack of integrated analysis tools for biomedical researchers. This project addresses this issue by (a) developing tools based on Bayesian statistics for the rigorous and reproducible analysis of experimental DEER data, providing comprehensive methods for uncertainty quantification (error bars) in DEER data, and (b) creating advanced computational tools to utilize DEER data in the refinement of protein structures based on atomic-resolution ensemble models. Overall, the goal of the project is to significantly accelerate the workflow of DEER data analysis, interpretation and modeling and increase its rigor, reproducibility and accessibility. This will enable the study of the structure and dynamics of larger and more complex proteins and protein assemblies, which are increasingly important in biomedical research.