Modeling Macromolecular Complexes: A Journey Across Scales

While proteins and nucleic acids are the fundamental components of an organism, Biology itself is based on the interactions they make with each other. Analyzing macromolecular interactions typically requires handling systems involving from two to hundreds of polypeptide chains. After a brief overview of the modeling challenges faced in computational structural biology, this chapter presents concepts and tools aiming at improving our understanding of the link between the static structures of macromolecular complexes and their biophysical/biological properties. We discuss geometrical approaches suited to atomic-resolution complexes and to large protein assemblies; for each, we also present examples of their successful application in quantifying and interpreting biological data. This methodology includes state-of-the-art geometric analyses of surface area, volume, curvature, and topological properties (isolated components, cavities, voids, cycles) related to Voronoï constructions in the context of structure analysis. On the applied side, we present novel insights into real biological problems gained thanks to these modeling tools.