Combinatorial docking for multi-molecular assembly and protein structure prediction

Yuval Inbar & Haim J. Wolfson, Tel Aviv University.

  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 multi-molecular assemblies.
  We apply it to predict both quaternary structures of oligomers and multi-proteins complexes. Moreover, adapting the algorithm to consider backbone connectivity, we also show that it may be useful in the prediction of protein tertiary structures when the structures of the protein parts are available. This application was tested both on domain assembly in order to predict the spatial arrangement of domains in multi-domain proteins, and on protein building blocks (substructures of domains with relatively high population times) assembly to predict their arrangement within a domain in the native protein