Biological dynamics for protein properties and functions

项目摘要/摘要 蛋白质动力学对其生物学功能至关重要。与分子生物学相结合，最先进的 飞秒光谱和计算模拟，生物过程现在可以从 初始超快动力学到随后在最基本水平上的长时间运动，从而使分子 机制是可以揭示的。我们最近研究了几个 自然界中的生物光机械，如光酶和光感受器。我们制定了完整的 用光酶光解实时修复DNA中紫外线损伤的胸腺嘧啶二聚体的光循环，包括 十步超快基元反应，揭示了一个统一的电子转移分子机理 光解酶超家族。在另一个方向上，我们也在理解 水-蛋白质相互作用和动力学，并阐明了水化之间的基本耦合运动 皮秒时间尺度上的水和蛋白质侧链，提供了水化水的直接环境 控制侧链波动。对生物水的认识对各种生物的研究具有重要意义 蛋白质识别和酶催化等活性。在这一新的、协同的努力中，我们接受挑战 为了探索更多新的复杂体系，主要在三个方面：(1)研究了一种复杂的 (6-4)-光解酶和一种新发现的脂肪酸光脱羧酶来绘制整个 酶反应，揭示了完整的催化光循环。这两种光合酶在性质上都对 修复紫外线损伤的DNA，生产碳氢生物燃料；(2)检测紫外线的三个光感受器 UVR8、蓝光隐色素(DmCry和AtCry)和几种红光光敏色素揭示初级 初始信号和后续构象变化的动力学。整个动态过程可以 从超快飞秒到长时间毫秒；(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、动态性和功能性。我们将系统地研究巨型行星中的空穴-水动力学。 伴侣蛋白(GroEL)用于了解滞留水在底物蛋白质折叠中的作用。我们会 增加飞秒X射线自由电子激光(XFEL)技术的新的强大方法和高水平 量子力学/分子力学(QM/MM)的计算。我们将开发新的 概念和重大发现。我们正在探索的这些前沿领域将为 进一步的生物医学应用。

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.