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Technology Topics Modeling

Modeling with SAXS

PSI-SGKB [doi:10.1038/th_psisgkb.2008.12]
Technical Highlight - October 2008
Short description: J. Mol. Biol. 382, 1089-1106 (2008)

Steps in the refinement of a model using SAXS data. At the top are shown the various scoring functions used, and at the bottom the initial model (left) and the refined model (right) are shown.

Obtaining structural information about a protein is highly desirable but not always straightforward. X-ray crystallography and NMR spectroscopy provide accurate high-resolution structures, but their use can be limited by protein purification difficulties or problems with crystallization or the protein's size. Single-particle electron microscopy has provided exciting insights but does not yield atomic-resolution structures. Computational protein structure prediction methods are often limited by their accuracy.

Small-angle X-ray scattering (SAXS) is more versatile but provides only low-resolution information about the shape of a macromolecule or a complex in solution. It is extremely rapid, requiring only seconds to minutes to process the data. It also has the advantage that it can be used on a wide range of assemblies, from DNA fragments to whole virions.

SAXS data can aid computational modeling of proteins in two ways. One, it can be used to chose between different models, particularly for quaternary structure arrangements. And two, SAXS profiles can be used during the model-building stage.

Förster et al. have now integrated SAXS profiles into their software to produce a SAXS module within their Integrative Modeling Platform (IMP), a program for modeling proteins and their assemblies.

They used 12 simulated examples to assess their method, and then moved on to test their software against experimental data. They produced a model of the quaternary structure of the homotetramer D-xylose isomerase (XI) based on an experimental SAXS profile. It correctly determined the quaternary arrangement of the four subunits of the XI momoner from the SAXS profile and a high accuracy subunit model based on 67% sequence identity with the template structure.

Förster et al. conclude that SAXS profiles can play a useful role in modeling quaternary structure, particularly if the information is integrated with other data. Pieces of information that seem relatively uninformative by themselves can together give accurate and precise models of proteins and assemblies.

Maria Hodges

References

  1. Forster Friedrich, Webb Benjamin, Krukenberg Kristin A, Tsuruta Hiro, Agard David A et al. Integration of small-angle X-ray scattering data into structural modeling of proteins and their assemblies.
    J Mol Biol 382, 1089-1106 (2008). doi:10.1016/j.jmb.2008.07.074

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