Modeling of Multimolecular Complexes

Macromolecular complexes play a key role in cellular function. Predicting the structure and dynamics of these complexes is one of the key challenges in structural biology. Docking applications have traditionally been used to predict pairwise interactions between proteins. However, few methods exist for modeling multi-protein assemblies. Here we present two methods, CombDock and DockStar, that can predict multi-protein assemblies starting from subunit structural models. CombDock can assemble subunits without any assumptions about the pairwise interactions between subunits, while DockStar relies on the interaction graph or, alternatively, a homology model or a cryo-electron microscopy (EM) density map of the entire complex. We demonstrate the two methods using RNA polymerase II with 12 subunits and TRiC/CCT chaperonin with 16 subunits.