Super-Resolution in Solution X-Ray Scattering and Its Applications to Structural Systems Biology

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. Expected final online publication date for the Annual Review of Biophysics Volume 42 is May 06, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.