@article{Vangone2015, 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.}, author = {Vangone, Anna and Bonvin, Alexandre Mjj J. J.}, doi = {10.7554/elife.07454}, journal = {eLife}, month = {jul}, title = {Contacts-based prediction of binding affinity in protein–protein complexes}, url = {https://doi.org/10.7554/elife.07454}, volume = {4}, year = {2015} }