Methods for SAXS-Based Structure Determination of Biomolecular Complexes

Measurements from small-angle X-ray scattering (SAXS) are highly informative to determine the structures of bimolecular complexes in solution. Here, current and recent SAXS-driven developments are described, with an emphasis on computational modeling. In particular, accurate methods to computing one theoretical scattering profile from a given structure model are discussed, with a key focus on structure factor coarse-graining and hydration contribution. Methods for reconstructing topological structures from an experimental SAXS profile are currently under active development. We report on several modeling tools designed for conformation generation that make use of either atomic-level or coarse-grained representations. Furthermore, since large, flexible biomolecules can adopt multiple well-defined conformations, a traditional single-conformation SAXS analysis is inappropriate, so we also discuss recent methods that utilize the concept of ensemble optimization, weighing in on the SAXS contributions of a heterogeneous mixture of conformations. These tools will ultimately posit the usefulness of SAXS data beyond a simple space-filling approach by providing a reliable structure characterization of biomolecular complexes under physiological conditions.