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Biological Systems: Imaging Dynamics & Function

 

The cell is the fundamental unit of life, and understanding biological processes at a cellular level requires detailed knowledge of the structure and dynamics of large macromolecular machines. Currently lacking are the tools necessary for dynamic imaging of such interacting complexes in operation, in native environments, and at the nanoscale.

NGLS X-ray lasers will revolutionize small- and wide-angle X-ray scattering (SAXS, WAXS) for dynamics structure determination by providing exposure times much faster than rotational diffusion times. High-speed SAXS and WAXS scattering snapshots will reveal a wealth of additional structural information (contained in modulations or fluctuations in the nominally radially symmetric SAXS signal) and associated dynamics of macromolecular machines and interacting complexes (e.g., novel drugs acting a membrane proteins).

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Once built, NGLS will further revolutionize structural studies by providing ~1010 diffraction snapshots per day. Combined with advanced analytical techniques, this capability will elucidate the role of heterogeneity in biological systems; enable 4-D imaging of molecular machines; and provide unprecedented, statistically validated access to the operation of molecular factories. The ability to acquire large numbers of snapshots for multiple conformations will revolutionize structural biology.