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.