Protein Allostery and Catalysis Beyond Bragg Diffraction

摘要 这个项目的中心目标是了解蛋白质运动是如何产生功能的。然而，可视化 运动中的蛋白质是结构生物学中一个固有的困难问题，因为它涉及许多来自 构象。为了应对这一挑战，我们采取了跨学科的方法。我们将我们的理解应用于 基于散射的结构方法理论为处理和处理开发新的计算方法 解释代表构象无序的数据。我们已经开发了提取动态信息的方法- 来自蛋白质晶体的信息，具有激活晶体结构的潜力，我们已经绘制了 变构酶和柔性酶的结构相互转化。在未来几年，我们将继续致力于 关于蛋白质变构和催化的分子机制的基本问题，为了解决这个问题，我们将 通过将低温电子显微镜(CRYO-EM)与先进的X射线方法相结合来扩大我们的工作范围。 我们的目标是：捕捉变构网络中的相关运动，应用我们的专业知识进行数学分解 构象异质性的问题，以及(3)探测控制催化的蛋白质运动。

Abstract The central goal of this project is to understand how protein motion gives rise to function. However, visualizing proteins in motion is a problem that is inherently difficult in structural biology as it involves signals from many conformations. To tackle this challenge, we take an interdisciplinary approach. We apply our understanding of the theory of scattering-based structural methods to develop new computational methods for processing and interpretating data representing conformational disorder. We have developed methods to extract dynamic infor- mation from protein crystals that have the potential to animate crystal structures, and we have mapped the structural interconversions of allosteric and flexible enzymes. In the coming years, we will continue to tackle fundamental questions about the molecular mechanisms of protein allostery and catalysis, and to do so, we will expand the scope of our work by integrating cryo-electron microscopy (cryo-EM) with advanced X-ray methods. Our goals are to: capture correlated motions in allosteric networks, apply our expertise with mathematical de- composition to the problem of conformational heterogeneity, and (3) probe protein motions that control catalysis.