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Characterizing the morphology of protein binding patches

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Title Characterizing the morphology of protein binding patches
 
Creator MALOD-DOGNIN, N
BANSAL, A
CAZALS, F
 
Subject protein complex
binding patch
interface morphology
structural comparisons
voronoi models
shelling tree
tree edit distance
dynamic programming-based comparisons
TREE EDIT DISTANCE
COMPUTATIONAL DESIGN
RECOGNITION SITES
SCORING FUNCTIONS
INTERFACES
DOCKING
ALGORITHM
SURFACE
IMMUNOGLOBULINS
IDENTIFICATION
 
Description Let the patch of a partner in a protein complex be the collection of atoms accounting for the interaction. To improve our understanding of the structurefunction relationship, we present a patch model decoupling the topological and geometric properties. While the geometry is classically encoded by the atomic positions, the topology is recorded in a graph encoding the relative position of concentric shells partitioning the interface atoms. The topologicalgeometric duality provides the basis of a generic dynamic programming-based algorithm comparing patches at the shell level, which may favor topological or geometric features. On the biological side, we address four questions, using 249 cocrystallized heterodimers organized in biological families. First, we dissect the morphology of binding patches and show that Nature enjoyed the topological and geometric degrees of freedom independently while retaining a finite set of qualitatively distinct topological signatures. Second, we argue that our shell-based comparison is effective to perform atomic-level comparisons and show that topological similarity is a less stringent than geometric similarity. We also use the topological versus geometric duality to exhibit topo-rigid patches, whose topology (but not geometry) remains stable upon docking. Third, we use our comparison algorithms to infer specificity-related information amidst a database of complexes. Finally, we exhibit a descriptor outperforming its contenders to predict the binding affinities of the affinity benchmark. The softwares developed with this article are available from http://team.inria.fr/abs/vorpatch_compatch/.
 
Publisher WILEY-BLACKWELL
 
Date 2014-10-15T16:56:14Z
2014-10-15T16:56:14Z
2012
 
Type Article
 
Identifier PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 80(12)2652-2665
http://dx.doi.org/10.1002/prot.24144
http://dspace.library.iitb.ac.in/jspui/handle/100/15265
 
Language en