Structural modeling of proteins by integrating small-angle x-ray scattering data

Elucidating the structure of large biomolecules such as multi-domain proteins or protein complexes is challenging due to their high flexibility in solution. Recently, an “integrative structural biology” approach has been proposed, which aims to determine the protein structure and characterize protein flexibility by combining complementary high-and low-resolution experimental data using computer simulations. Small-angle x-ray scattering (SAXS) is an efficient technique that can yield low-resolution structural information, including protein size and shape. Here, we review computational methods that integrate SAXS with other experimental datasets for structural modeling. Finally, we provide a case study of determination of the structure of a protein complex formed between the tandem SH3 domains in c-Cb1-associated protein and the proline-rich loop in human vinculin.