The role of circular dichroism spectroscopy in the era of integrative structural biology

Circular dichroism (CD) spectroscopy has been used widely in structural biology for literally a half century, primarily to examine the secondary structure, folding, and interactions of proteins in solution. With recent developments in instrumentation, it is now possible to apply CD to many additional types of sample environments, including oriented membranes, films, and dehydrated samples. In addition, developments in bioinformatics have made validated CD spectra and metadata available for novel analysis methods on additional types of samples such as membrane proteins, intrinsically disordered proteins, multiple fold types, and multicomponent, macromolecular complexes. New software has also enabled increased inter-operability of CD with other structural biology methodologies, contributing to their use in joint studies of protein structures at various levels of organization.