May 30, 2014
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.
Figure: Schematic setup for SAXS data collection. There are two routine options available. A typical one is to use a programmable pump that allows a flow-cell setup for X-ray exposure and subsequent data acquisition for both a biological sample and its corresponding buffer. The other is a chromatography-coupled setup with a size exclusion column (SEC) that is designed to remove unwanted species. The location of a homogeneous sample along the elution can be identified via a real-time (Equation (4), together with chromatography light absorbance. A final one-dimensional scattering profile I(q) is obtained after buffer subtraction.
Results from: Yang S. Methods for SAXS-based Structure Determination of Biomolecular Complexes. Advanced Materials. 2014:n/a-n/a. doi: 10.1002/adma.201304475.