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InterPepScore: a deep learning score for improving the FlexPepDock refinement protocol
Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-1696-0183
Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-3772-8279
2022 (English)In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 38, no 12, p. 3209-3215Article in journal (Refereed) Published
Abstract [en]

Motivation: Interactions between peptide fragments and protein receptors are vital to cell function yet difficult to experimentally determine in structural details of. As such, many computational methods have been developed to aid in peptide-protein docking or structure prediction. One such method is Rosetta FlexPepDock which consistently refines coarse peptide-protein models into sub-Angstrom precision using Monte-Carlo simulations and statistical potentials. Deep learning has recently seen increased use in protein structure prediction, with graph neural networks used for protein model quality assessment. Results: Here, we introduce a graph neural network, InterPepScore, as an additional scoring term to complement and improve the Rosetta FlexPepDock refinement protocol. InterPepScore is trained on simulation trajectories from FlexPepDock refinement starting from thousands of peptide-protein complexes generated by a wide variety of docking schemes. The addition of InterPepScore into the refinement protocol consistently improves the quality of models created, and on an independent benchmark on 109 peptide-protein complexes its inclusion results in an increase in the number of complexes for which the top-scoring model had a DockQ-score of 0.49 (Medium quality) or better from 14.8% to 26.1%.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2022. Vol. 38, no 12, p. 3209-3215
National Category
Bioinformatics (Computational Biology)
Identifiers
URN: urn:nbn:se:liu:diva-185842DOI: 10.1093/bioinformatics/btac325ISI: 000805233700001PubMedID: 35575349OAI: oai:DiVA.org:liu-185842DiVA, id: diva2:1670822
Note

Funding Agencies|SeRC [VR 2020-03352, CTS 20:453]

Available from: 2022-06-16 Created: 2022-06-16 Last updated: 2023-12-28Bibliographically approved

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Johansson-Åkhe, IsakWallner, Björn

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