Integrative structural modeling with small angle X-ray scattering profiles

Abstract

Recent technological advances enabled high-throughput collection of Small Angle X-ray Scattering (SAXS) profiles of biological macromolecules. Thus, computational methods for integrating SAXS profiles into structural modeling are needed more than ever. Here, we review specifically the use of SAXS profiles for the structural modeling of proteins, nucleic acids, and their complexes. First, the approaches for computing theoretical SAXS profiles from structures are presented. Second, computational methods for predicting protein structures, dynamics of proteins in solution, and assembly structures are covered. Third, we discuss the use of SAXS profiles in integrative structure modeling approaches that depend simultaneously on several data types.

Figure 1

Theoretical SAXS profiles of glucose isomerase from five programs fitted against the experimental SAXS profile.

Figure 2

Yeast Nup145N (443–605) crystal structure [PDB:3kep] monomer (green) and dimer (red)versusthe solution SAXS profile (black).

Figure 3

FoXS-MES server output for ensemble fit (green) of the SAXS profile (black)versusa single conformation fit (red) for XLF-XRCC4 filaments. A) Fit plot, B) Residuals plot, and C) Ensemble structures and weights.

Figure 4

Comparative modeling and SAXS profile fitting using the Chimera visualization package. MODELLER was used to add missing residues and a His tag on the C-terminal domain of Nup133 (see sequence alignment in the upper right window). Three models were generated (red, green and blue) using a template structure [PDB:3KFO] (white). The FoXS interface (lower left window) was used to fit the profiles computed for the X-ray structure and the models to the experimental SAXS profile (lower right window). A) model window, B) sequence alignment window, C) model scores, D) FoXS interface window, and E) FoXS output window.

Figure 5

FoXS-MES ensemble fit (green) of the SAXS profile (black)versusa single conformation fit (red) for Mre11-Rad50. A) Fit plot, B) Residuals plot, and C) Ensemble structures and weights.

Figure 6

Docking models with similar shapes generate similar profiles. A) Top 10 docking models for adrenodoxin reductase-adrenodoxin complex [PDB:1E6E], and B) top 20 docking models for PAPS reductase-thioredoxin complex [PDB:2O8V].