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（通过应用来证明）：蛋白质动力学是生物学功能。揭示。酶促催化 另一个方向，我们还对修复紫外线受损的DNA进行了重要意义，并完全映射了轮胎过程，在局部分子水平上响起一系列超快基本反应，完整的鸡蛋囊光循环，并为诸如理性设计的分子基础提供了分子基础，例如治疗护肤者。 （2）检查蓝光的加密型和紫外线受体UVR8的两个重要光感受器是一个发现的蓝光光感受器。在受体中，从对生物 - 水动力学和光循环的努力中获得的哭泣机制和光循环的过程对于蛋白质特性uninvione univition unive protint of tocution unive protinal of tocution unive univie对于精神障碍等一系列S的药物设计至关重要。