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Annu Rev Biophys. 2013;42:415-41. doi: 10.1146/annurev-biophys-083012-130301. Epub 2013 Mar 11.

Super-resolution in solution X-ray scattering and its applications to structural systems biology.

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Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.


Small-angle X-ray scattering (SAXS) is a robust technique for the comprehensive structural characterizations of biological macromolecular complexes in solution. Here, we present a coherent synthesis of SAXS theory and experiment with a focus on analytical tools for accurate, objective, and high-throughput investigations. Perceived SAXS limitations are considered in light of its origins, and we present current methods that extend SAXS data analysis to the super-resolution regime. In particular, we discuss hybrid structural methods, illustrating the role of SAXS in structure refinement with NMR and ensemble refinement with single-molecule FRET. High-throughput genomics and proteomics are far outpacing macromolecular structure determinations, creating information gaps between the plethora of newly identified genes, known structures, and the structure-function relationship in the underlying biological networks. SAXS can bridge these information gaps by providing a reliable, high-throughput structural characterization of macromolecular complexes under physiological conditions.

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