Perspectives on solution-based small angle X-ray scattering for protein and biological macromolecule structural biology

Abstract

Small-angle X-ray scattering (SAXS) is used to extract structural information from a wide variety of non-crystalline samples in different fields (<i>e.g.</i>, materials science, physics, chemistry, and biology). This review provides an overview of SAXS as applied to structural biology, specifically for proteins and other biomacromolecules in solution with an emphasis on extracting key structural parameters and the interpretation of SAXS data using a diverse array of techniques. These techniques cover aspects of building and assessing models to describe data measured from monodispersed and ideal dilute samples through to more complicated structurally polydisperse systems. <i>Ab initio</i> modelling, rigid body modelling as well as normal-mode analysis, molecular dynamics, mixed component and structural ensemble modelling are discussed. Dealing with polydispersity both physically in terms of component separation as well as approaching the analysis and modelling of data of mixtures and evolving systems are described, including methods for data decomposition such as single value decomposition/principle component analysis and evolving factor analysis. This review aims to highlight that solution SAXS, with the cohort of developments in data analysis and modelling, is well positioned to build upon the traditional 'single particle view' foundation of structural biology to take the field into new areas for interpreting the structures of proteins and biomacromolecules as population-states and dynamic structural systems.