Ultrafast time resolved protein X-ray crystallography

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We now have all the tools and the methodology that allows us to watch proteins function with structural resolution in real time with ultrafast time resolution, probing fundamental processes in biological activation. With the availability of femtosecond X-ray Free Electron Laser sources which now operate in the hard X-ray regime with femtosecond pulse duration, unique opportunities arise to gain fundamental new insight into ultrafast structural processes in proteins. Here, I propose a research programme on femtosecond time-resolved X-ray crystallography of light induced reactions in light sensitive protein crystals and supporting spectroscopic studies. The necessary preliminary work for such experiments are provided in the form of data collected at the Stanford Linac Coherent Light Source (LCLS), from ultrafast optical spectroscopy investigations of non-linear transitions and pulse shaping to control femtosecond population transfer performed in the home laboratory, and from supporting modeling of crystallographic data quality based on measured source parameters. In addition to the primary target, which is a femtosecond experiment with Photoactive Yellow Protein crystals, novel experiments are being developed firstly using picosecond synchrotron sources, to add to the existing choices for femtosecond pump-probe studies and focuses on photoswitchable fluorescent proteins.