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PeSTo: parameter-free geometric deep learning for accurate prediction of protein binding interfaces

18 Apr 2023Nature Communications 2023 4archive 2025-07-28

Lucien F. Krapp, Luciano A. Abriata, Fabio Cortés Rodriguez, Matteo Dal Peraro

Proteins are essential molecular building blocks of life, responsible for most biological functions as a result of their specific molecular interactions. However, predicting their binding interfaces remains a challenge. In this study, we present a geometric transformer that acts directly on atomic coordinates labeled only with element names. The resulting model—the Protein Structure Transformer, PeSTo—surpasses the current state of the art in predicting protein-protein interfaces and can also predict and differentiate between interfaces involving nucleic acids, lipids, ions, and small molecules with high confidence. Its low computational cost enables processing high volumes of structural data, such as molecular dynamics ensembles allowing for the discovery of interfaces that remain otherwise inconspicuous in static experimentally solved structures. Moreover, the growing foldome provided by de novo structural predictions can be easily analyzed, providing new opportunities to uncover unexplored biology.

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Antibody-antigen binding prediction

Results from the paper archive 2025-07-28

TaskDatasetModelMetricValueRank at snapshotLeaderboardReport
Antibody-antigen binding prediction MIPE Pesto AUC-PR 0.724 #3 of 7 Archive leaderboard report
Antibody-antigen binding prediction MIPE Pesto AUC-ROC 0.856 #3 of 7 Archive leaderboard report

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