article Open Access (gold) EN 2015-07-20

Contacts-based prediction of binding affinity in protein–protein complexes

eLife, Vol. 4, pp. e07454–e07454 (2015)

Utrecht University

DOI: 10.7554/elife.07454 PMID: 26193119

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Abstract

Almost all critical functions in cells rely on specific protein-protein interactions. Understanding these is therefore crucial in the investigation of biological systems. Despite all past efforts, we still lack a thorough understanding of the energetics of association of proteins. Here, we introduce a new and simple approach to predict binding affinity based on functional and structural features of the biological system, namely the network of interfacial contacts. We assess its performance against a protein-protein binding affinity benchmark and show that both experimental methods used for affinity measurements and conformational changes have a strong impact on prediction accuracy. Using a subset of complexes with reliable experimental binding affinities and combining our contacts and contact-types-based model with recent observations on the role of the non-interacting surface in protein-protein interactions, we reach a high prediction accuracy for such a diverse dataset outperforming all other tested methods.

Topics

Protein Structure and Dynamics 1.00 Bioinformatics and Genomic Networks 0.99 Computational Drug Discovery Methods 0.99

Field: Biochemistry, Genetics and Molecular Biology · Subfield: Molecular Biology

Keywords

Affinities,Protein–protein interaction,Binding affinities,Computational biology,Benchmark (surveying),Surface protein,Plasma protein binding,Structural biology,Protein structure,Chemistry

MeSH Terms

Molecular BiologyMolecular BiologyMolecular BiologyMolecular BiologyProtein BindingProtein BindingProtein BindingProtein Binding

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