{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T19:18:54Z","timestamp":1772047134395,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013981","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","award":["POC 101185627"],"award-info":[{"award-number":["POC 101185627"]}],"id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biorad"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The specific region of an antibody responsible for binding to an antigen, known as the paratope, is essential for immune recognition. Accurate identification of this small yet critical region can accelerate the development of therapeutic antibodies. Determining paratope locations typically relies on modeling the antibody structure, which is computationally intensive and difficult to scale across large antibody repertoires. We introduce Paraplume, a sequence-based paratope prediction method that leverages embeddings from protein language models (PLMs), without the need for structural input and achieves superior performance across multiple benchmarks compared to current methods. In addition, reweighting PLM embeddings using Paraplume predictions yields more informative sequence representations, improving downstream tasks such as binder classification and epitope binning. Applied to large antibody repertoires, Paraplume reveals that antigen-specific somatic hypermutations are associated with larger paratopes, suggesting a potential mechanism for affinity enhancement. Our findings position PLM-based paratope prediction as a powerful, scalable alternative to structure-dependent approaches, opening new avenues for understanding antibody evolution.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013981","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T18:43:46Z","timestamp":1771440226000},"page":"e1013981","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paraplume: A fast and accurate antibody paratope prediction method provides insights into repertoire-scale binding dynamics"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4668-884X","authenticated-orcid":true,"given":"Gabriel","family":"Ath\u00e8nes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Woolfe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5456-9361","authenticated-orcid":true,"given":"Thierry","family":"Mora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2686-5702","authenticated-orcid":true,"given":"Aleksandra M.","family":"Walczak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"pcbi.1013981.ref001","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bej.2018.06.003","article-title":"Understanding and overcoming trade-offs between antibody affinity, specificity, stability and solubility","volume":"137","author":"LA Rabia","year":"2018","journal-title":"Biochem Eng J."},{"issue":"9","key":"pcbi.1013981.ref002","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1001\/jama.2020.1166","article-title":"Estimated research and development investment needed to bring a new medicine to market 2009 -2018","volume":"323","author":"OJ Wouters","year":"2020","journal-title":"JAMA."},{"issue":"2","key":"pcbi.1013981.ref003","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s40484-019-0172-y","article-title":"Progress in molecular docking","volume":"7","author":"J Fan","year":"2019","journal-title":"Quant Biol."},{"issue":"1","key":"pcbi.1013981.ref004","doi-asserted-by":"crossref","DOI":"10.1016\/j.str.2019.10.011","article-title":"Modeling antibody-antigen complexes by information-driven docking","volume":"28","author":"F Ambrosetti","year":"2020","journal-title":"Structure."},{"issue":"10","key":"pcbi.1013981.ref005","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.1038\/s41596-021-00597-z","article-title":"A practical guide to large-scale docking","volume":"16","author":"BJ Bender","year":"2021","journal-title":"Nat Protoc."},{"issue":"8016","key":"pcbi.1013981.ref006","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"J Abramson","year":"2024","journal-title":"Nature."},{"key":"pcbi.1013981.ref007","doi-asserted-by":"crossref","unstructured":"Hitawala FN, Gray JJ. 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