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BMC Bioinformatics

, 9:447

First Online: 21 October 2008Received: 10 June 2008Accepted: 21 October 2008


BackgroundThe study of protein-protein interactions is becoming increasingly important for biotechnological and therapeutic reasons. We can define two major areas therein: the structural prediction of protein-protein binding mode, and the identification of the relevant residues for the interaction so called -hot-spots-. These hot-spot residues have high interest since they are considered one of the possible ways of disrupting a protein-protein interaction. Unfortunately, large-scale experimental measurement of residue contribution to the binding energy, based on alanine-scanning experiments, is costly and thus data is fairly limited. Recent computational approaches for hot-spot prediction have been reported, but they usually require the structure of the complex.

ResultsWe have applied here normalized interface propensity NIP values derived from rigid-body docking with electrostatics and desolvation scoring for the prediction of interaction hot-spots. This parameter identifies hot-spot residues on interacting proteins with predictive rates that are comparable to other existing methods up to 80% positive predictive value, and the advantage of not requiring any prior structural knowledge of the complex.

ConclusionThe NIP values derived from rigid-body docking can reliably identify a number of hot-spot residues whose contribution to the interaction arises from electrostatics and desolvation effects. Our method can propose residues to guide experiments in complexes of biological or therapeutic interest, even in cases with no available 3D structure of the complex.

AbbreviationsNIPnormalized interface propensity

ASAaccessible solvent area

ASPatomic solvation parameters

ODAoptimal docking area

PPVpositive predictive value


SEC3staphylococcal enterotoxin C3

HELhen egg lysozyme


BPTIbovine pancreatic trypsin inhibitor

Im2immunity protein 2

AchRacetylcholine receptor.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2105-9-447 contains supplementary material, which is available to authorized users.

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Autor: Solène Grosdidier - Juan Fernández-Recio


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