Prediction of multimolecular assemblies by multiple docking

The majority of proteins function when associated in multimolecular assemblies. Yet, prediction of the structures of multimolecular complexes has largely not been addressed, probably due to the magnitude of the combinatorial complexity of the problem. Docking applications have traditionally been used to predict pairwise interactions between molecules. We have developed an algorithm that extends the application of docking to multimolecular assemblies. We apply it to predict quaternary structures of both oligomers and multi-protein complexes. The algorithm predicted well a near-native arrangement of the input subunits for all cases in our data set, where the number of the subunits of the different target complexes varied from three to ten. In order to simulate a more realistic scenario, unbound cases were tested. In these cases the input conformations of the subunits are either unbound conformations of the subunits or a model obtained by a homology modeling technique. The successful predictions of the unbound cases, where the input conformations of the subunits are different from their conformations within the target complex, suggest that the algorithm is robust. We expect that this type of algorithm should be particularly useful to predict the structures of large macromolecular assemblies, which are difficult to solve by experimental structure determination.