Wide-angle X-ray solution scattering as a probe of ligand-induced conformational changes in proteins

A chemical genetics approach to functional analysis of gene products utilizes high-throughput target-based screens of compound libraries to identify ligands that modulate the activity of proteins of interest. Candidates are further screened using functional assays designed specifically for the protein--and function--of interest, suffering from the need to customize the assay to each protein. An alternative strategy is to utilize a probe to detect the structural changes that usually accompany binding of a functional ligand. Wide-angle X-ray scattering from proteins provides a means to identify a broad range of ligand-induced changes in secondary, tertiary, and quaternary structure. The speed and accuracy of data acquisition, combined with the label-free targets and binding conditions achievable, indicate that WAXS is well suited as a moderate-throughput assay in the detection and analysis of protein-ligand interactions.