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（由适用提供）：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femtoseocnd光谱和计算模拟，现在可以研究生物学动力学，从Intial Ultrafast运动到最基本的长期波动。因此，可以揭示分子机制。我们最近研究了水 - 蛋白质相互作用的动力学和机制，并阐明了在皮秒时间尺度上发生的基本水 - 蛋白偶联运动，这是弥合超快大量水运动和慢速蛋白质波动之间差距的理想时间。对生物水的理解对于多种生物学活性（例如蛋白质 - 配体/药物识别和酶促催化）具有重要意义。 另一个方向，我们还在修复紫外线损坏的DNA方面取得了重大进展，并实时彻底绘制了整个修复过程，包括一系列超快基本反应。我们在当地分子水平上阐明了完整的维修照片，并为潜在的应用提供了分子基础，例如用于治愈皮肤癌的合理药物设计。在这项新的，协同的努力中，我们结合了内在连接的参与方向，并计划在（1）研究蛋白质-DNA和蛋白质 - 蛋白质蛋白质络合物的互化水动力学的两个主要领域探索更复杂的系统，以深入了解与生物学功能和（2）次数的蓝色功能和动态功能的深度理解，并获得了（2）次要效果的动态波动。受体UVR8。加密色素是最近发现的蓝光光感受器，可调节动物（和植物）中的昼夜节律，植物和UVR8的生长和发育是一种新的UV-照片感应器，它触发信号转导的信号转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，我们将发现初始信号转导的主要过程，并揭示加密斑块和UVR8的反应机理和照片。从这些对生物 - 水动力学和光感受器光启的努力中获得的新知识对于涉及蛋白质 - DNA/蛋白质复合物和信号转导过程的蛋白质特性，动力学和功能至关重要，更重要的是，对于药物设计对于一系列疾病的实际应用至关重要。