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

项目总结： 蛋白质的内在机制--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。与生物相关的运动是 潜在地相当微妙，广泛分布在三级结构中，并可能涵盖广泛的时间范围 比例。目前的生物物理方法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。在这里，我们建议 解决这一问题的一种全新的方法，涉及将强电场应用于蛋白质晶体 利用同步时间分辨X射线衍射仪观察产生的运动的空间和时间细节。 初步工作为这种称为EF/TRX的方法的开发和应用提供了强有力的理由， 并激发了一系列有趣的实验，以探索这种方法在揭示结构 复杂蛋白质功能的基础。EF/TRX涉及相当大的技术和概念创新，但 这里描述的工作的完成应该使科学工作者能够广泛地使用这种新方法 社区，并刺激进一步发展。更根本的是，提出的实验将为 为理解蛋白质功能的力学基础奠定基础。

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.