3D Structural Modeling of the Interactome Protein interaction networks are a principal component of a systems level description of the cell. Network topology has been clearly linked to protein function, expression dynamics and other genomic features. However, most network studies thus far operate on a relatively high level of abstraction and treat all proteins as simple nodes and all interactions as simple edges, neglecting the structural and chemical aspects of each interaction. We utilize atomic-resolution information from 3D protein structures to further characterize proteins and interactions in the network, thereby giving a chemical reality to nodes and edges. This differentiation also helps to resolve the current debate on the correlation between a proteins degree and its evolutionary rate, as only multi-interface hubs appear to evolve slower than the average protein. Finally, we show that current models of network evolution can only explain the topology of interactions sharing the same interface, while they fail to explain the growth of multi-interface proteins, and they likely need to be revisited. More details