Contacts-based Prediction of Binding Affinity in Protein-protein Complexes

Overview

Journal Elife

Specialty Biology

Date 2015 Jul 21

PMID 26193119

Citations 223

Authors

Anna Vangone

Alexandre Mjj Bonvin

Affiliations

Soon will be listed here.

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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