Structural modeling of proteins integrating small-angle X-ray scattering data
【摘要】：Structure elucidation of a large biomolecule, such as a multi-domain protein or protein complex, is generally challenging due to its high flexibility in solution. Recently, a notion of "integrative structural biology" has been proposed, which aims to determine the protein structure and characterize its 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 like the size and shape of the protein. For very flexible protein or protein complex, a screening-after-sampling strategy is often used to elucidate the ensemble properties of these systems. In this category of approaches, a pool of structural models starting from high resolution structures obtained by X-ray or NMR is produced, and then the structures are screened out of the pool to best fit the SAXS data. We have investigated solution structures of several proteins, such as the triple-BRCT-domain of epithelial cell transforming protein 2, the tandem WW domains of the forming binding protein 21 and the tandem SH3 domains of CAP in complex with the proline rich loop of vinculin.