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

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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.

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Anna Vangone

Computational Structural Biology group, Bijvoet Center for Biomolecular Research, Faculty of Science - Chemistry, Utrecht University, Utrecht, Netherlands

Competing interests
The authors declare that no competing interests exist.
Alexandre M J J Bonvin

Computational Structural Biology group, Bijvoet Center for Biomolecular Research, Faculty of Science - Chemistry, Utrecht University, Utrecht, Netherlands

For correspondence
a.m.j.j.bonvin@uu.nl

Competing interests
The authors declare that no competing interests exist.

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