Systems biology requires accurate models of protein complexes, including physical interactions that assemble and regulate these molecular machines. Yeast two-hybrid (Y2H) and affinity-purification/mass-spectrometry (AP-MS) technologies measure different protein-protein relationships, and issues of completeness, sensitivity and specificity fuel debate over which is best for high-throughput interactome data collection. Static graphs currently used to model Y2H and AP-MS data neglect dynamic and spatial aspects of macromolecular complexes and pleiotropic protein function.