Ultrafast Biological Dynamics for Protein Properties and Functions

蛋白质性质和功能的超快生物动力学

• 批准号: 9079081
• 负责人: DONGPING ZHONG
• 金额: $ 19.45万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9079081
• 关键词: Affect; Animals; Area; Award; Binding; Biochemistry; Biological; Biological Process; Catalysis; Complex; Coupling; DNA; Disease; Drug Design; Growth and Development function; Investigation; Knowledge; Lasers; Ligands; Light; Maps; Mental disorders; Methods; Molecular; Molecular Biology; Motion; Nature; Neurodegenerative Disorders; Pharmaceutical Preparations; Photoreceptors; Plants; Process; Property; Protein Dynamics; Proteins; Reaction; Research; Research Personnel; Series; Signal Transduction; Skin Cancer; Spectrum Analysis; System; Time; UV induced DNA damage; Ultraviolet Rays; Water; base; circadian pacemaker; cryptochrome; flexibility; interfacial; mental disorder prevention; novel; plant growth/development; practical application; prevent; protein complex; protein function; public health relevance; receptor; repaired; response; simulation; ultraviolet damage

 DESCRIPTION (provided by applicant): Protein dynamics is essentail for its biological function. With integration of molecular biology, state-of-the-art femtoseocnd spectroscopy and computation simulations, the biological dynamics now can be studied from the intial ultrafast motions to longtime fluctuations on the most fundamental level. The molecular mechanisms thus can be revealed. We have recently investigated the dynamics and mechanism of water-protein interactions and elucidated the fundamental water-protein coupling motions occurring on the picosecond time scales, an ideal timscale to bridge the gap between ultrafast bulk-water motions and slow protein fluctuations. The understanding of biological water is significant to a variety of biological activites such as protein-ligand/drug recognition and enzymatic catalysis. In another direction, we also made significant advances on repair of UV-damaged DNA and completely mapped out the entire repair process in real time, including a series of ultrafast elementary reactions. We elucidate the complete repair photocycles at the local molecular level and provide a molecular basis for potential applciations such as rational drug design for curing skin cancer. In this new, synergistic effort, we combine the intrinsically connected reseach directions and plan to take challenging to explore more complex systems on two major areas of (1) investigating interfacial water dynamis at protein-DNA and protein-protein complexes to gain the deep understanding of binding properties and dynamic fluctuations of complexes for biological functions and (2) examining two important photoreceptors of blue-light cryptochrome and UV-light receptor UVR8. The cryptochrome is a recently discovered blue-light photoreceptor that regulates the circadian clock in animals (and plants) and growth and development in plants and UVR8 is a new UV-photoreceptor that triggers signal transduction to protect UV damage. By systematic investigations of these dynamics in receptors, we will uncover the primary process of initial signal transduction and reveal the reaction mechanisms and photocycles of cryptochrome and UVR8. The new knowledge obtained from these efforts on biological-water dynamics and photoreceptor photocycles is significant to protein properties, dynamics, and functions involving protein-DNA/protein complexes and signal transduction processes, and more importantly, is critical to practical applications of drug design for a series of diseases such as mental disorder.

 描述（由申请人提供）：蛋白质动力学对其生物学功能是必需的。随着分子生物学、飞秒激光光谱学和计算机模拟技术的结合，生物动力学的研究从最初的超快运动到最基本的长期涨落都可以进行。从而揭示了分子机制。我们最近研究了水-蛋白质相互作用的动力学和机制，并阐明了发生在皮秒时间尺度上的基本水-蛋白质耦合运动，这是一个理想的时间尺度，可以弥合超快体水运动和缓慢蛋白质波动之间的差距。生物水的研究对于蛋白质-配体/药物识别、酶催化等生物活性的研究具有重要意义。在 在另一个方向上，我们还在修复紫外线损伤的DNA方面取得了重大进展，并在真实的时间内完全绘制了整个修复过程，包括一系列超快基元反应。我们在局部分子水平上阐明了完整的修复光周期，并为潜在的应用提供了分子基础，如治疗皮肤癌的合理药物设计。在这一新的协同努力中，我们将联合收割机这两个相互联系的研究方向结合起来，并计划在两个主要领域进行更具挑战性的探索，即（1）研究蛋白质-DNA和蛋白质-蛋白质复合物的界面水动力学，以深入了解复合物的结合特性和生物功能的动力学波动;（2）研究两种重要的蓝光受体，光隐花色素和紫外光受体UVR 8。隐花色素是最近发现的一种蓝光光感受器，可调节动物（和植物）的昼夜节律钟以及植物的生长和发育，而UVR 8是一种新的紫外光感受器，可触发信号传导以保护紫外线损伤。通过对受体中这些动力学的系统研究，我们将揭示初始信号转导的主要过程，并揭示隐花色素和UVR 8的反应机制和光循环。从这些工作中获得的生物水动力学和光感受器光循环的新知识是重要的蛋白质的性质，动力学，并涉及蛋白质-DNA/蛋白质复合物和信号转导过程的功能，更重要的是，是至关重要的药物设计的一系列疾病，如精神疾病的实际应用。