Seeing Protein Mechanics: The Link Between Molecular Structure, Function, and Evolution

了解蛋白质力学：分子结构、功能和进化之间的联系

• 批准号: 9756416
• 负责人: RAMA RANGANATHAN
• 金额: $ 40.5万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-07 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756416
• 关键词: Address; Amino Acids; Biochemistry; Biological; Biology; Charge; Chemicals; Communities; Complex; Coupled; Crystallization; Crystallography; Data; Data Analyses; Data Analytics; Development; Disease; Engineering; Environment; Evolution; Formulation; Foundations; Goals; Health; Life; Link; Measures; Mechanics; Mediating; Methods; Molecular; Molecular Conformation; Molecular Machines; Molecular Structure; Motion; NMR Spectroscopy; Nuclear; Nuclear Magnetic Resonance; Pattern; Problem Solving; Process; Protein Conformation; Proteins; Resolution; Risk; Route; Structural Protein; Structure; Testing; Time; Work; X ray diffraction analysis; X-Ray Crystallography; biophysical techniques; chemical reaction; chromophore; electric field; experimental study; innovation; man; novel; novel strategies; physical model; protein complex; protein function; protein structure; protein structure function; simulation; theories; tool

Project Summary: The internal mechanics of proteins – the coordinated motion of amino acids and the pattern of forces constraining these motions – connects protein structure and function. The biologically relevant motions are potentially quite subtle, distributed widely over the tertiary structure, and likely to cover a broad range of time scales. Current biophysical methods do not offer a route to a complete description of these motions, a problem that severely limits our understanding of protein structure, function, and evolution. Here, we propose a completely new approach to this problem involving the application of strong electric fields to protein crystals with simultaneous time-resolved x-ray diffraction to observe the resulting motions in spatial and temporal detail. Preliminary work provides strong justification for development and application of this method, called EF/TRX, and motivates a set of interesting experiments to explore the power of this approach for exposing the structural basis for complex protein functions. EF/TRX involves considerable technical and conceptual innovations, but the completion of the work described here should enable broad usage of this new method by the scientific community and stimulate further development. More fundamentally, the experiments proposed will lay the foundation for understanding the mechanical basis of protein function.

项目概要： 蛋白质的内部机制-氨基酸的协调运动和力的模式 限制这些运动-连接蛋白质的结构和功能。生物学上相关的运动是 可能相当微妙，广泛分布在三级结构中，并且可能覆盖广泛的时间范围 鳞片目前的生物物理学方法并没有提供一条完整描述这些运动的途径， 这个问题严重限制了我们对蛋白质结构、功能和进化的理解。在此，我们建议 一个全新的方法来解决这个问题，包括将强电场应用于蛋白质晶体 同时进行时间分辨的X射线衍射，以观察空间和时间细节的所产生的运动。 初步工作为开发和应用这种称为EF/TRX的方法提供了强有力的理由， 并激发了一系列有趣的实验来探索这种方法的力量， 复杂蛋白质功能的基础。EF/TRX涉及大量的技术和概念创新， 这里所描述的工作的完成将使科学家能够广泛使用这种新方法。 社区，促进进一步发展。更重要的是，提出的实验将奠定 理解蛋白质功能的机械基础。