Biological dynamics for protein properties and functions

项目概要/摘要 蛋白质动力学对其生物学功能至关重要。结合分子生物学，最先进的 飞秒光谱学和计算模拟，现在可以从以下方面研究生物过程 最初的超快动力学到随后最基本水平上的长时间运动，从而分子 机制可以被揭示。我们最近研究了一些动力学和机制 自然界中的生物光机器，例如光酶和光感受器。我们制定了完整的 通过光酶光解作用实时修复 DNA 中受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，并揭示了统一的电子转移分子机制 光解酶超家族。在另一个方向上，我们在理解上也取得了重大进展。 水-蛋白质相互作用和动力学，并阐明了水合作用之间的基本耦合运动 皮秒时间尺度上的水和蛋白质侧链，提供了水合水的直接证据 控制侧链波动。对生物水的认识对于多种生物具有重要意义 蛋白质识别和酶催化等活动。在这一新的协同努力中，我们迎接挑战 在三个主要领域探索更多新的复杂系统：（1）研究复杂的两种光酶 (6-4)-光产物光裂合酶和新发现的脂肪酸光脱羧酶绘制出整个 酶促反应并揭示完整的催化光循环。两种光酶本质上都具有重要意义 修复紫外线损伤的 DNA 并生产碳氢化合物生物燃料； (2) 检查紫外光的三个感光器 UVR8、蓝光隐花色素（DmCry 和 AtCry）和几种红光光敏色素可揭示主要成分 初始信号传导和随后的构象变化的动力学。整个动态过程可能 发生从超快飞秒到长时间毫秒； (3)进一步探索水-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。我们将系统地研究巨型物体中的空腔-水动力学 伴侣蛋白 (GroEL) 用于了解底物蛋白折叠功能中的截留水。我们会 添加飞秒 X 射线自由电子激光器 (XFEL) 技术和高水平新的强大方法 这些研究中的量子力学/分子力学（QM/MM）计算。我们将开发新的 概念并做出重要发现。我们正在追求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.