{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:44:07Z","timestamp":1766159047145,"version":"3.41.2"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Australia\/Cure Cancer Australia","award":["GNT1184339","GNT1157298"],"award-info":[{"award-number":["GNT1184339","GNT1157298"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Over 300\u00a0000 protein\u2013protein interaction (PPI) pairs have been identified in the human proteome and targeting these is fast becoming the next frontier in drug design. Predicting PPI sites, however, is a challenging task that traditionally requires computationally expensive and time-consuming docking simulations. A major weakness of modern protein docking algorithms is the inability to account for protein flexibility, which ultimately leads to relatively poor results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here, we propose DockNet, an efficient Siamese graph-based neural network method which predicts contact residues between two interacting proteins. Unlike other methods that only utilize a protein\u2019s surface or treat the protein structure as a rigid body, DockNet incorporates the entire protein structure and places no limits on protein flexibility during an interaction. Predictions are modeled at the residue level, based on a diverse set of input node features including residue type, surface accessibility, residue depth, secondary structure, pharmacophore and torsional angles. DockNet is comparable to current state-of-the-art methods, achieving an area under the curve (AUC) value of up to 0.84 on an independent test set (DB5), can be applied to a variety of different protein structures and can be utilized in situations where accurate unbound protein structures cannot be obtained.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>DockNet is available at https:\/\/github.com\/npwilliams09\/docknet and an easy-to-use webserver at https:\/\/biosig.lab.uq.edu.au\/docknet. All other data underlying this article are available in the article and in its online supplementary material.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac797","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T14:33:01Z","timestamp":1670596381000},"source":"Crossref","is-referenced-by-count":13,"title":["DockNet: high-throughput protein\u2013protein interface contact prediction"],"prefix":"10.1093","volume":"39","author":[{"given":"Nathan P","family":"Williams","sequence":"first","affiliation":[{"name":"STEM College, RMIT University , Melbourne, VIC, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-6401","authenticated-orcid":false,"given":"Carlos H M","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Computational Biology and Clinical Informatics, Baker Heart and Diabetes Institute , Melbourne, VIC, Australia"},{"name":"School of Chemistry and Molecular Biosciences, University of Queensland , Brisbane, QLD, Australia"}]},{"given":"Jia","family":"Truong","sequence":"additional","affiliation":[{"name":"STEM College, RMIT University , Melbourne, VIC, Australia"}]},{"given":"David B","family":"Ascher","sequence":"additional","affiliation":[{"name":"Computational Biology and Clinical Informatics, Baker Heart and Diabetes Institute , Melbourne, VIC, Australia"},{"name":"School of Chemistry and Molecular Biosciences, University of Queensland , Brisbane, QLD, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8735-2871","authenticated-orcid":false,"given":"Jessica K","family":"Holien","sequence":"additional","affiliation":[{"name":"STEM College, RMIT University , Melbourne, VIC, Australia"}]}],"member":"286","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"2023010805394523100_btac797-B1","doi-asserted-by":"crossref","first-page":"e1000807","DOI":"10.1371\/journal.pcbi.1000807","article-title":"Protein\u2013protein interactions essentials: key concepts to building and analyzing interactome networks","volume":"6","author":"De Las Rivas","year":"2010","journal-title":"PLoS Comput. Biol"},{"key":"2023010805394523100_btac797-B2","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1021\/ja026939x","article-title":"HADDOCK:\u2009 a protein\u2212protein docking approach based on biochemical or biophysical information","volume":"125","author":"Dominguez","year":"2003","journal-title":"J. Am. Chem. Soc"},{"key":"2023010805394523100_btac797-B3","doi-asserted-by":"crossref","first-page":"40959","DOI":"10.1074\/jbc.M302926200","article-title":"The staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease","volume":"278","author":"Filipek","year":"2003","journal-title":"J. Biol. Chem"},{"key":"2023010805394523100_btac797-B4","first-page":"6533","volume-title":"Protein Interface Prediction Using Graph Convolutional Networks","author":"Fout","year":"2017"},{"key":"2023010805394523100_btac797-B5","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0092-8674(00)81823-1","article-title":"Crystal structure of human cyclophilin a bound to the amino-terminal domain of HIV-1 capsid","volume":"87","author":"Gamble","year":"1996","journal-title":"Cell"},{"key":"2023010805394523100_btac797-B6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.12688\/f1000research.3-47.v2","article-title":"J. FeatureViewer, a BioJS component for visualization of position-based annotations in protein sequences","volume":"3","author":"Garcia","year":"2014","journal-title":"F1000Res"},{"key":"2023010805394523100_btac797-B7","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1186\/1471-2105-9-447","article-title":"Identification of hot-spot residues in protein-protein interactions by computational docking","volume":"9","author":"Grosdidier","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2023010805394523100_btac797-B8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1073\/pnas.93.1.13","article-title":"Principles of protein-protein interactions","volume":"93","author":"Jones","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023010805394523100_btac797-B9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.pbiomolbio.2015.01.009","article-title":"Flexibility and small pockets at protein-protein interfaces: new insights into druggability","volume":"119","author":"Jubb","year":"2015","journal-title":"Prog. Biophys. Mol. Biol"},{"key":"2023010805394523100_btac797-B10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/prot.340090106","article-title":"Distribution and complementarity of hydropathy in mutisunit proteins","volume":"9","author":"Korn","year":"1991","journal-title":"Proteins: Struct. Funct. Bioinformatics"},{"key":"2023010805394523100_btac797-B11","doi-asserted-by":"crossref","first-page":"W233","DOI":"10.1093\/nar\/gkn216","article-title":"The RosettaDock server for local protein-protein docking","volume":"36","author":"Lyskov","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2023010805394523100_btac797-B12","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1093\/bioinformatics\/bty419","article-title":"NGL viewer: web-based molecular graphics for large complexes","volume":"34","author":"Rose","year":"2018","journal-title":"Bioinformatics"},{"key":"2023010805394523100_btac797-B13","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/bioinformatics\/bty647","article-title":"BIPSPI: a method for the prediction of partner-specific protein\u2013protein interfaces","volume":"35","author":"Sanchez-Garcia","year":"2019","journal-title":"Bioinformatics"},{"first-page":"15642","year":"2019","author":"Townshend","key":"2023010805394523100_btac797-B14"},{"key":"2023010805394523100_btac797-B15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1251\/bpo16","article-title":"Yeast two-hybrid: state of the art","volume":"2","author":"Van Criekinge","year":"1999","journal-title":"Biol. Proced. Online"},{"key":"2023010805394523100_btac797-B16","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1016\/j.jmb.2015.07.016","article-title":"Updates to the integrated protein-protein interaction benchmarks: docking benchmark version 5 and affinity benchmark version 2","volume":"427","author":"Vreven","year":"2015","journal-title":"J. Mol. Biol"},{"key":"2023010805394523100_btac797-B17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/nar\/28.1.289","article-title":"DIP: the database of interacting proteins","volume":"28","author":"Xenarios","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2023010805394523100_btac797-B18","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1093\/bioinformatics\/btab761","article-title":"Deep graph learning of inter-protein contacts","volume":"38","author":"Xie","year":"2021","journal-title":"Bioinformatics"},{"key":"2023010805394523100_btac797-B19","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10930-007-9108-x","article-title":"Characterization of protein-protein interfaces","volume":"27","author":"Yan","year":"2008","journal-title":"Protein J"},{"key":"2023010805394523100_btac797-B20","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/pro.5560030501","article-title":"A role for surface hydrophobicity in protein-protein recognition","volume":"3","author":"Young","year":"1994","journal-title":"Protein Sci"},{"key":"2023010805394523100_btac797-B21","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1093\/bioinformatics\/btw533","article-title":"PPI4DOCK: large scale assessment of the use of homology models in free docking over more than 1000 realistic targets","volume":"32","author":"Yu","year":"2016","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btac797\/48342569\/btac797.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btac797\/48520718\/btac797.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btac797\/48520718\/btac797.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T05:40:06Z","timestamp":1673156406000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btac797\/6885444"}},"subtitle":[],"editor":[{"given":"Lenore","family":"Cowen","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btac797","relation":{},"ISSN":["1367-4811"],"issn-type":[{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2023,1,1]]},"published":{"date-parts":[[2022,12,9]]},"article-number":"btac797"}}