title: X-ray lasers for structural and dynamic biology.
abstract: Research opportunities and techniques are reviewed for the application of hard x-ray pulsed free-electron lasers (XFEL) to structural biology. These include the imaging of protein nanocrystals, single particles such as viruses, pump--probe experiments for time-resolved nanocrystallography, and snapshot wide-angle x-ray scattering (WAXS) from molecules in solution. The use of femtosecond exposure times, rather than freezing of samples, as a means of minimizing radiation damage is shown to open up new opportunities for the molecular imaging of biochemical reactions at room temperature in solution. This is possible using a 'diffract-and-destroy' mode in which the incident pulse terminates before radiation damage begins. Methods for delivering hundreds of hydrated bioparticles per second (in random orientations) to a pulsed x-ray beam are described. New data analysis approaches are outlined for the correlated fluctuations in fast WAXS, for protein nanocrystals just a few molecules on a side, and for the continuous x-ray scattering from a single virus. Methods for determining the orientation of a molecule from its diffraction pattern are reviewed. Methods for the preparation of protein nanocrystals are also reviewed. New opportunities for solving the phase problem for XFEL data are outlined. A summary of the latest results is given, which now extend to atomic resolution for nanocrystals. Possibilities for time-resolved chemistry using fast WAXS (solution scattering) from mixtures is reviewed, toward the general goal of making molecular movies of biochemical processes.
authors.affiliation: Department of Physics, Arizona State University, Tempe, AZ 85287, USA. spence@asu.edu
authors.forename: J C H
authors.initials: JC
authors.lastname: Spence
authors.forename: U
authors.initials: U
authors.lastname: Weierstall
authors.forename: H N
authors.initials: HN
authors.lastname: Chapman
mesh_terms: D001695:Biology / Q000295:instrumentation* / Q000639:trends*; D007834:Lasers; D014965:X-Rays