Abstract
Over the last years, large scale proteomics studies have generated a wealth of information of biomolecular complexes. Adding the structural dimension to the resulting interactomes represents a major challenge that classical structural experimental methods alone will have difficulties to confront. To meet this challenge, complementary modeling techniques such as docking are thus needed. Among the current docking methods, HADDOCK (High Ambiguity-Driven DOCKing) distinguishes itself from others by the use of experimental and/or bioinformatics data to drive the modeling process and has shown a strong performance in the critical assessment of prediction of interactions (CAPRI), a blind experiment for the prediction of interactions. Although most docking programs are limited to binary complexes, HADDOCK can deal with multiple molecules (up to six), a capability that will be required to build large macromolecular assemblies. We present here a novel web interface of HADDOCK that allows the user to dock up to six biomolecules simultaneously. This interface allows the inclusion of a large variety of both experimental and/or bioinformatics data and supports several types of cyclic and dihedral symmetries in the docking of multibody assemblies. The server was tested on a benchmark of six cases, containing five symmetric homo-oligomeric protein complexes and one symmetric protein-DNA complex. Our results reveal that, in the presence of either bioinformatics and/or experimental data, HADDOCK shows an excellent performance: in all cases, HADDOCK was able to generate good to high quality solutions and ranked them at the top, demonstrating its ability to model symmetric multicomponent assemblies. Docking methods can thus play an important role in adding the structural dimension to interactomes. However, although the current docking methodologies were successful for a vast range of cases, considering the variety and complexity of macromolecular assemblies, inclusion of some kind of experimental information (e.g. from mass spectrometry, nuclear magnetic resonance, cryoelectron microscopy, etc.) will remain highly desirable to obtain reliable results.
Highlights
Over the last years, large scale proteomics studies have generated a wealth of information of biomolecular complexes
We have compiled a benchmark of six multimer assemblies
In one case (1URZ), the starting structures correspond to the dimeric form of the complex, whereas the trimeric form had to be predicted; this complex corresponds to a viral envelope protein that was a target in critical assessment of prediction of interactions (CAPRI)
Summary
Large scale proteomics studies have generated a wealth of information of biomolecular complexes. Adding the structural dimension to the resulting interactomes represents a major challenge that classical structural experimental methods alone will have difficulties to confront To meet this challenge, complementary modeling techniques such as docking are needed. Many of the most important functions in the cell are carried out by large, dynamic molecular assemblies, such as the ribosome, the proteasome, the spliceosome, RNA polymerases, and the nuclear pore complex [4, 5] For such assemblies, high resolution methods such as x-ray crystallography and NMR spectroscopy often provide atomic level information at the level of individual subunits or subcomplexes, but they typically encounter difficulties at the level of the full complex. Once the composition of the complex is known, there is a variety of experimental techniques available to ob-
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