Protein Allostery and Catalysis Beyond Bragg Diffraction

布拉格衍射之外的蛋白质变构和催化

• 批准号: 10406516
• 负责人: Nozomi Ando
• 金额: $ 41.56万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406516
• 关键词: Catalysis; Computing Methodologies; Cryoelectron Microscopy; Crystallization; Data; Disease; Enzymes; Goals; Heterogeneity; Life; Maps; Mathematics; Methods; Molecular; Molecular Conformation; Motion; Proteins; Roentgen Rays; Signal Transduction; Structure; Ursidae Family; Work; base; flexibility; interdisciplinary approach; structural biology; theories

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.

抽象的 该项目的核心目标是了解蛋白质运动如何产生功能。但是，可视化 运动中的蛋白质是一个在结构生物学中固有困难的问题，因为它涉及许多人的信号 构象。为了应对这一挑战，我们采取了跨学科的方法。我们应用了我们对的理解 基于散射的结构方法的理论开发了用于处理和处理的新计算方法 解释代表构象障碍的数据。我们开发了提取动态信息的方法 来自具有动画晶体结构的潜力的蛋白质晶体的交流，我们已经映射了 变构和柔性酶的结构互连。在未来几年中，我们将继续解决 关于蛋白质变构和催化的分子机制的基本问题，为此，我们将 通过将冷冻电子显微镜（Cryo-EM）与先进的X射线方法集成在一起，扩大我们工作的范围。 我们的目标是：捕获变构网络中的相关动作，将我们的专业知识应用于数学方面 构象异质性问题的组成，以及（3）控制催化的探针蛋白运动。