Rapid accumulation of experimental data on protein-protein complexes drives the paradigm shift in protein docking from "traditional," template free approaches to template based techniques. Homology docking algorithms based on sequence similarity between target and template complexes can account for up to 20% of known protein-protein interactions. When highly homologous templates for the target complex are not available, but the structure of the target monomers is known, docking by local structural alignment may provide an adequate solution. Such an algorithm was developed based on the structural comparison of monomers to cocrystallized interfaces. A library of the interfaces was generated from cocrystallized protein-protein complexes in PDB. The partial structure alignment algorithm was validated on the DOCKGROUND benchmark sets. The optimal performance of the partial (interface) structure alignment was achieved with the interface residues defined by 12 Å distance across the interface. Overall, the partial structure alignment yielded more accurate models than the full structure alignment. Most templates identified by the partial structure alignment had low sequence identity to the target, which makes them hard to detect by sequence-based methods. The results indicate that the structure alignment techniques provide a much needed addition to the docking arsenal, with the combined structure alignment and template free docking success rate significantly surpassing that of the free docking alone.
© 2010 Wiley-Liss, Inc.