Integrative Structural Biology

Integrative approaches using data from a wide variety of methods are yielding model structures of complex biological assemblies. Biological assemblies and machines often elude structural characterization, hampering our understanding of how they function, how they evolved, and how they can be modulated. A number of macromolecular assemblies have been reconstructed over the years by piecemeal efforts, such as fitting high-resolution crystal structures of individual components into lower-resolution electron microscopy (EM) reconstructions of the entire complex (1). Although notable successes have been achieved in this way, ambiguous or conflicting models can still arise (2–4). Thus, structural and computational biologists have been looking for new ways to put all of the pieces back together. Sophisticated integrative approaches are being developed (5, 6) that combine information from different types of experiments, physical theories, and statistical analyses to compute structural models of multicomponent assemblies and complex biological systems.