Abstract

Protein dynamics is a complex process and the current challenge is to break down its complexity into elementary processes which act on different time scales and length scales. We integrate femtosecond spectroscopy, molecular biology techniques, and computational simulations to study functional evolution in real time and thus elucidate the complex dynamics with unprecedented detail. Here, two important biological systems, protein surface hydration and light-driven DNA repair, will be reported. With femtosecond temporal and single-residue spatial resolution, we mapped out the global water motion in the hydration layer using intrinsic tryptophan residue to scan the protein surface with site-directed mutagenesis. The results reveal the ultrafast nature of surface hydration dynamics and provide a molecular basis for protein conformational flexibility, an essential determinant of protein function. For DNA repair, we followed the entire functional evolution through femtosecond synchronization. We resolved a series of ultrafast processes including active-site solvation, energy transfer, and electron tunneling. These results elucidate the crucial role of ultrafast dynamics in control of biological function efficiency and lay bare the molecular mechanism of DNA repair at atomic scale.