Biological dynamics for protein properties and functions

蛋白质特性和功能的生物动力学

• 批准号: 10330205
• 负责人: DONGPING ZHONG
• 金额: $ 46.72万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10330205
• 关键词: Area; Biochemical Reaction; Biological; Biological Process; Catalysis; Complex; Computer Simulation; Coupled; DNA; Disease; Electron Transport; Fatty Acids; Hydration status; Hydrocarbons; Knowledge; Lasers; Light; Maps; Mechanics; Methods; Molecular; Molecular Biology; Molecular Conformation; Motion; Nature; Photoreceptors; Phytochrome; Process; Property; Protein Dynamics; Proteins; Quantum Mechanics; Reaction; Role; Signal Transduction; Spectrum Analysis; System; Techniques; Thymine Dimers; Time; UV induced DNA damage; Ultraviolet Rays; Water; biological systems; chaperonin; complex biological systems; cryptochrome; frontier; millisecond; novel; protein folding; protein structure; repaired; ultraviolet damage; x-ray free-electron laser

Project Summary/Abstract Protein dynamics is essential for its biological function. With integration of molecular biology, state-of-the-art femtosecond spectroscopy and computation simulations, the biological processes now can be studied from the intial ultrafast dynamics to subsequent longtime motions on the most fundamental level and thus the molecular mechanisms can be revealed. We have recently investigated the dynamics and mechanisms of several biological photomachines such as photoenzymes and photoreceptors in nature. We mapped out the complete repair photocycles of UV-damaged thymine dimer in DNA by photoenzyme photolayses in real time, including ten steps of ultrafast elementary reactions, and reveled a unified electron-transfer molecular mechanism for photolyase superfamily. In another direction, we also made significant advances on the understanding of water-protein interactions and dynamics and elucidated the fundamental coupled motions between hydration water and protein sidechains on the picosecond time scales, providing direct envidence that hydration water controls sidechain fluctuations. The understanding of biological water is significant to a variety of biological activities such as protein recognition and enzymatic catalysis. In this new, synergistic effort, we take challenges to explore more new complex systems in three major areas: (1) investigating two photoenzymes of an intricate (6-4)-photoproduct photolyase and a newly discoivered fatty-acid photodecarboxylase to map out the entire enzymatic reactions and reveal complete catalytic photocycles. Both photoenzyems are significnat in nature to repair UV-damaged DNA and produce hydrocarbon biofuels; (2) examining three photoreceptors of UV-light UVR8, blue-light cryptochromes (DmCry and AtCry) and several red-light phytochromes to reveal the primary dynamics for initial signaling and subsequent conformational changes. The entire dynamic processes may occur from ultrafast femtoseconds to longtime milliseconds; (3) exploring further water-protein interactions and dynamics of complex biological systems for better understanding the role of water in protein structure, stability, dynamics and functions. We will systematically investigate the cavity-water dynamics in a giant chaperonin protein (GroEL) for understanding trapped water in function of substrate protein folding. We will add new powerful methods of the femtosecond x-ray free electron lasers (XFEL) technique and the high-level quantum mechanics/molecualr mechanics (QM/MM) calcualtions in these studies. We will develop new conceptes and make important discoveries. These frontiers we are pursuing will provide new knowledge for further biomedical applications.

项目摘要/摘要 蛋白质动力学对于其生物学功能至关重要。随着分子生物学的整合，最先进的 飞秒光谱和计算模拟，现在可以从研究中研究生物学过程 Intial超快动力学在最基本的水平上对随后的长期运动，因此分子 可以揭示机制。我们最近研究了几种的动态和机制 生物学光电，例如光酶和自然界中的光感受器。我们绘制了完整的 通过光酶光层实时（包括），包括 超快基本反应的十个步骤，并陶醉于统一的电子转移分子机制 光溶解酶超家族。在另一个方向上，我们还在理解方面取得了重大进步 水 - 蛋白质相互作用和动力学，并阐明了水合之间的基本耦合运动 皮秒时间尺度上的水和蛋白质Sidechains，提供了水合水的直接不满 控制侧链波动。对生物水的理解对于多种生物学意义重大 诸如蛋白质识别和酶促催化之类的活性。在这项新的，协同的努力中，我们应对挑战 在三个主要领域探索更多新的复杂系统：（1）研究两个复杂的光酶 （6-4） - 脂蛋白酶和新脱落的脂肪酸光二羧化酶，以绘制整个整个 酶促反应并揭示完整的催化光弹。两种光酶本质上都是重要的 修复紫外线受损的DNA并产生碳氢化合物生物燃料； （2）检查紫外线的三个光感受器 UVR8，蓝光加密色素（DMCRY和ATCRY）和几种红色植物色素，以揭示主要 初始信号传导和随后构象变化的动力学。整个动态过程可能 从超飞的飞秒到长时间的毫秒。 （3）探索进一步的水 - 蛋白质相互作用 和复杂生物系统的动力学，以更好地了解水在蛋白质结构中的作用， 稳定性，动力学和功能。我们将系统地研究巨型中的空腔 - 水动力学 伴侣蛋白（GROEL），用于理解底物蛋白折叠功能的捕获水。我们将 添加新的强大方法的飞秒X射线免费电子激光器（XFEL）技术和高级技术 在这些研究中，量子力学/分子力学（QM/mm）的钙化。我们将开发新的 概念并做出重要发现。我们追求的这些边界将为 进一步的生物医学应用。