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

项目摘要/摘要 本项目为鹿(双电子-电子)开发了新的计算分析和建模方法 共振)光谱学。鹿是一种定量测定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。蛋白质运动对许多关键分子来说是至关重要的 以人的生命和疾病为基础的过程。因此，鹿提供了重要的见解，有助于 到药物开发所需的知识库。结合X射线结晶学、核磁共振和X射线衍射仪 冷冻-EM，鹿是一套互补的综合实验生物结构工具的一部分。它是特别的 对膜蛋白的研究具有重要意义。该领域的一个主要障碍是缺乏综合分析工具 对生物医学研究人员来说。该项目通过(A)开发基于贝叶斯统计的工具来解决这一问题 为了对实验鹿数据进行严格和可重复性的分析，提供了全面的方法 鹿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 基于原子分辨率系综模型的蛋白质结构精细化中的Deer数据。总体而言， 该项目的目标是显著加快鹿数据分析、解释和建模的工作流程 并提高其严密性、可重复性和可及性。这将使研究结构和动力学成为可能。 更大、更复杂的蛋白质和蛋白质组件，它们在生物医学中越来越重要 研究。

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.