Macromolecular docking restrained by a small angle X-ray scattering profile

Dina Schneidman-Duhovny*, Michal Hammel, Andrej Sali

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


While many structures of single protein components are becoming available, structural characterization of their complexes remains challenging. Methods for modeling assembly structures from individual components frequently suffer from large errors, due to protein flexibility and inaccurate scoring functions. However, when additional information is available, it may be possible to reduce the errors and compute near-native complex structures. One such type of information is a small angle X-ray scattering (SAXS) profile that can be collected in a high-throughput fashion from a small amount of sample in solution. Here, we present an efficient method for protein-protein docking with a SAXS profile (FoXSDock): generation of complex models by rigid global docking with PatchDock, filtering of the models based on the SAXS profile, clustering of the models, and refining the interface by flexible docking with FireDock. FoXSDock is benchmarked on 124 protein complexes with simulated SAXS profiles, as well as on 6 complexes with experimentally determined SAXS profiles. When induced fit is less than 1.5Å interface Cα RMSD and the fraction residues of missing from the component structures is less than 3%, FoXSDock can find a model close to the native structure within the top 10 predictions in 77% of the cases; in comparison, docking alone succeeds in only 34% of the cases. Thus, the integrative approach significantly improves on molecular docking alone. The improvement arises from an increased resolution of rigid docking sampling and more accurate scoring.

Original languageAmerican English
Pages (from-to)461-471
Number of pages11
JournalJournal of Structural Biology
Issue number3
StatePublished - Mar 2011
Externally publishedYes

Bibliographical note

Funding Information:
We thank Hiro Tsuruta, David Agard, Bill Weis, and Dmitry Svergun for discussions about SAXS, as well as Ben Webb and Daniel Russel for help with IMP. DSD has been funded by the Weizmann Institute Advancing Women in Science Postdoctoral Fellowship. We acknowledge support from NIH R01 GM083960, NIH U54 RR022220, NIH PN2 EY016525, and Rinat (Pfizer) Inc. SIBYLS beamline at Lawrence Berkeley National Laboratory is supported by the DOE program Integrated Diffraction Analysis Technologies (IDAT). We are also grateful for computer hardware gifts from Ron Conway, Mike Homer, Intel, Hewlett-Packard, IBM, and Netapp.


  • Macromolecular assembly
  • Protein-protein docking
  • Small angle X-ray scattering (SAXS)


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