{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T20:59:19Z","timestamp":1781729959839,"version":"3.54.5"},"reference-count":99,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":47,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lingang Laboratory","award":["LGL-2615-04"],"award-info":[{"award-number":["LGL-2615-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics, yet early translation is often hindered by the perceived coupling between antibacterial potency and mammalian toxicity. This assumption complicates prioritization: highly active candidates are frequently suspected to be hemolytic, while existing multi-task predictors rarely reveal where selectivity resides in sequence space. Here, we present Multifunctional AMP Learning Engine (MAPLE), an interpretable dual-stream framework for AMP identification and systematic category-specific functional profiling across 14 activity categories directly from peptide sequences. MAPLE combines protein language model embeddings with explicit physicochemical descriptors, enabling robust task-specific prediction under severe label imbalance. Across the benchmark dataset and a sequence-non-overlapping independent validation set, MAPLE achieves consistently well-balanced performance, including on low-prevalence but clinically relevant endpoints. Building on this predictive basis, we conduct systematic k-mer enrichment to map motif-level selectivity and show that potency\u2013hemolysis coupling is motif-regime-dependent rather than universal. Motifs most strongly enriched for antibacterial activity exhibit reduced hemolytic overlap and occupy a physicochemical regime characterized by moderate cationicity, lower hydrophobicity, and higher amphipathicity. We further provide a proof-of-concept prioritization workflow leveraging antibacterial-selective motifs, with structural modeling yielding conformations consistent with amphipathic \u03b1-helices. Despite limitations of predominantly binary annotations and incomplete structural integration, MAPLE offers reproducible sequence-level hypotheses and prioritization principles to support the engineering of potent and safer AMPs.<\/jats:p>","DOI":"10.1093\/bib\/bbag318","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:47:58Z","timestamp":1779882478000},"source":"Crossref","is-referenced-by-count":0,"title":["MAPLE: interpretable deep learning identifies selective antimicrobial peptides using joint evolutionary\u2013physicochemical analysis"],"prefix":"10.1093","volume":"27","author":[{"given":"Hao","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism, China Pharmaceutical University , No. 24 Tongjiaxiang, Gulou District, Nanjing 210009 ,","place":["China"]},{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University , No. 639 Longmian Avenue, Jiangning District, Nanjing 211198 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism, China Pharmaceutical University , No. 24 Tongjiaxiang, Gulou District, Nanjing 210009 ,","place":["China"]},{"name":"Institute of Innovative Drug, China Pharmaceutical University , No. 639 Longmian Avenue, Jiangning District, Nanjing 211198 ,","place":["China"]},{"name":"National Key Laboratory for Novel Software Technology, Nanjing University , No. 163 Xianlin Avenue, Qixia District, Nanjing 210023 ,","place":["China"]},{"name":"School of Artificial Intelligence, Nanjing University , No. 163 Xianlin Avenue, Qixia District, Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyu","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University , No. 639 Longmian Avenue, Jiangning District, Nanjing 211198 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University , No. 639 Longmian Avenue, Jiangning District, Nanjing 211198 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University , No. 639 Longmian Avenue, Jiangning District, Nanjing 211198 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangji","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism, China Pharmaceutical University , No. 24 Tongjiaxiang, Gulou District, Nanjing 210009 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Chuan","family":"Zhan","sequence":"additional","affiliation":[{"name":"National Key Laboratory for Novel Software Technology, Nanjing University , No. 163 Xianlin Avenue, Qixia District, Nanjing 210023 ,","place":["China"]},{"name":"School of Artificial Intelligence, Nanjing University , No. 163 Xianlin Avenue, Qixia District, Nanjing 210023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism, China Pharmaceutical University , No. 24 Tongjiaxiang, Gulou District, Nanjing 210009 ,","place":["China"]},{"name":"Institute of Innovative Drug, China Pharmaceutical University , No. 639 Longmian Avenue, Jiangning District, Nanjing 211198 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6685-2167","authenticated-orcid":false,"given":"Guo","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism, China Pharmaceutical University , No. 24 Tongjiaxiang, Gulou District, Nanjing 210009 ,","place":["China"]},{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University , No. 639 Longmian Avenue, Jiangning District, Nanjing 211198 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"2026061716450201500_ref1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Antimicrobial resistance C. 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