Shelling the Voronoi interface of protein-protein complexes predicts residue activity and conservation

Nature Precedings 01/2008;
Source: OAI


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.

Download full-text


Available from: Raik Grünberg, Sep 30, 2015
8 Reads
  • Source
    • "Others are specialized to study cavities and pockets in large biological molecules [10] [11] [12]. Solvation shells [13] [14] and the boundary region between proteins are also studied [15] [16]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A simple formalism is proposed for a quantitative analysis of interatomic voids inside and outside of a molecule in solution. It can be applied for the interpretation of volumetric data, obtained in studies of protein folding in water. The method is based on the Voronoi-Delaunay tessellation of molecular-dynamic models of solutions. It is suggested to select successive Voronoi shells, starting from the interface between the solute molecule and the solvent, and continuing to the outside (into the solvent) as well as into the inner of the molecule. Similarly, successive Delaunay layers, consisting of Delaunay simplexes, can also be calculated. Geometrical properties of the selected shells and layers are discussed. The behavior of inner and outer voids is discussed by the example of a molecular-dynamic model of an aqueous solution of the polypeptide hIAPP.
    Voronoi Diagrams in Science and Engineering (ISVD), 2012 Ninth International Symposium on; 01/2012
  • [Show abstract] [Hide abstract]
    ABSTRACT: An interesting property of the Voronoi tessellation is studied in the context of its application to the analysis of hydration shells in computer simulation of solutions. Namely the shells around a randomly chosen cell in a Voronoi tessellation attract extra volume from outside. There is a theoretical result which says that the mean volume of the first shell around a randomly chosen cell is greater than the anticipated value. The paper investigates this phenomenon for Voronoi tessellations constructed for computer models of point patterns with different variability of the Voronoi cell volumes (Poisson point process, RSA systems of hard spheres and molecular dynamics models of water). It analyzes also the subsequent shells, and proposes formulas for the mean shell volumes for all shell numbers. The obtained results are of value in calculations of the contribution of hydration of water to the “apparent” volume of the solutes.
    Seventh International Symposium on Voronoi Diagrams in Science and Engineering, ISVD 2010, Quebec, Canada, June 28-30, 2010; 01/2010
Show more