Biological dynamics for protein properties and functions

项目总结/摘要 蛋白质动力学对其生物学功能至关重要。随着分子生物学的整合，最先进的 飞秒光谱学和计算模拟，生物过程现在可以研究从 从最初的超快动力学到随后的最基本水平上的长期运动， 机制可以揭示。我们最近研究了几种 生物光机器，如自然界中的光酶和光感受器。我们制定了完整的 通过光酶光解，真实的时间修复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，我们也取得了重大进展， 水-蛋白质相互作用和动力学，阐明了水化之间的基本耦合运动 水和蛋白质侧链在皮秒的时间尺度上，提供了直接的证据， 控制侧链波动。生物水的认识对各种生物学意义重大 活性，如蛋白质识别和酶催化。在这一新的协同努力中， 在三个主要方面探索更多新的复杂系统：（1）研究一个复杂系统的两种光酶 （6-4）-光产物光裂合酶和一种新发现的脂肪酸光脱羧酶， 酶促反应，并揭示完整的催化光循环。这两种光酶在自然界中对 修复紫外线损伤的DNA并生产碳氢生物燃料;（2）检测紫外线的三种光感受器 UVR 8，蓝光隐花色素（DmCry和AtCry）和几种红光光敏色素，以揭示主要的 初始信号传导和随后的构象变化的动力学。整个动态过程可以 发生从超快飞秒到长毫秒;（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。我们将系统地研究一个巨大的 伴侣蛋白（GroEL），用于了解底物蛋白质折叠功能中的截留水。我们将 增加了飞秒x射线自由电子激光（XFEL）技术和高水平的新的强大的方法， 量子力学/分子力学（QM/MM）计算。发展新型 并有重大发现。我们所追求的这些前沿将为我们提供新的知识， 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.