Shelling the Voronoi interface of protein-protein complexes predicts residue activity and conservation
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- INRIA Sophia-Antipolis, Algorithms-Biology-Structure project, Sophia-Antipolis, France
- EMBL-CRG Systems Biology Unit, CRG--Centre de Regulacio Genomica, Barcelona, Spain
- Unité de Bioinformatique Structurale, Pasteur Institute, Paris, France
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This manuscript is a preprint. A published version is available at:
10.1002/prot.22381 (Peer Reviewed) Published in Proteins: Structure, Function, and Bioinformatics, Volume 76 Issue 3, Pages 677 - 692- Document Type:
- Manuscript
- Date:
- Received 21 June 2008 07:12 UTC; Posted 23 June 2008
- Subjects:
- Chemistry, Molecular Cell Biology, Bioinformatics
- Abstract:
The accurate description and analysis of protein-protein interfaces remains a challenging task. Traditional definitions, based on atomic contacts or changes in solvent accessibility, tend to over- or underpredict the interface itself and cannot discriminate active from less relevant parts.
We here extend a fast, parameter-free and purely geometric definition of protein interfaces and introduce the shelling order of Voronoi facets as a novel measure for an atom’s depth inside the nterface. Our analysis of 54 protein-protein complexes reveals a strong correlation between Voronoi Shelling Order (VSO) and water dynamics. High Voronoi Shelling Order coincides with residues that were found shielded from bulk water fluctuations in a recent molecular dynamics study. Yet, VSO predicts such “dry” residues at dramatically reduced cost and without consideration of forcefields or dynamics.
More central interface positions are often also increasingly enriched for hydrophobic residues. Yet, this hydrophobic centering is not universal and does not mirror the far stronger geometric bias of water fluxes. The seemingly complex water dynamics at protein interfaces appears thus largely controlled by geometry. Sequence analysis supports the functional relevance of both dry residues and residues with high VSO, both of which tend to be more conserved. However, upon closer inspection, the spatial distribution of conservation argues against the arbitrary dissection into core or rim and thus refines previous results. Voronoi Shelling Order reveals clear geometric patterns in protein interface composition, function and dynamics and facilitates the comparative analysis of protein-protein interactions.
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- This document is licensed to the public under the Creative Commons Attribution 3.0 License
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Bouvier, Benjamin, Grünberg, Raik, Nilges, Michael, and Cazals, Frederic. Shelling the Voronoi interface of protein-protein complexes predicts residue activity and conservation. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1522.2> (2008)
- Version info:
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Published version:
10.1002/prot.22381 (Peer Reviewed) Published in Proteins: Structure, Function, and Bioinformatics, Volume 76 Issue 3, Pages 677 - 692 -
Other versions of this document in Nature Precedings
Version number Document title Date v1 Posted 16 January 2008 Other versions of this document elsewhere on the web
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