Ultrafast Biological Dynamics for Protein Properties and Functions

 描述(申请人提供)：蛋白质动力学是其生物学功能所必需的。分子生物学、最先进的飞秒光谱学和计算模拟相结合，现在可以在最基本的水平上研究从初始超快运动到长期波动的生物动力学。因此，可以揭示其分子机制。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，可以弥合超快的整体水运动和缓慢的蛋白质波动之间的差距。了解生物水对蛋白质-配体/药物识别、酶催化等多种生物活性具有重要意义。在……里面 另一方面，我们还在紫外线损伤的DNA修复方面取得了重大进展，并实时完整地绘制了整个修复过程，包括一系列超快的基元反应。我们在局部分子水平上阐明了完整的修复光循环，并为合理设计治疗皮肤癌的药物等潜在应用提供了分子基础。在这一新的、协同的努力中，我们结合了内在联系的研究方向，并计划在以下两个主要领域探索更复杂的系统：(1)研究蛋白质-DNA和蛋白质-蛋白质复合体的界面水动力学，以深入了解生物功能复合体的结合性质和动态波动；(2)检测蓝光隐花色素和紫外光受体UVR8这两个重要的光受体。隐花色素是最近发现的一种蓝光感受器，它调节动物(和植物)的生物钟和植物的生长发育，而UVR8是一种新的紫外光感受器，它触发信号转导来保护紫外线损伤。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UVR8的反应机制和光循环。从生物-水动力学和光感受器光周期方面获得的新知识对蛋白质的性质、动力学和涉及蛋白质-DNA/蛋白质复合体和信号转导过程的功能具有重要意义，更重要的是，对于治疗一系列疾病(如精神障碍)的药物设计的实际应用至关重要。

 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.