{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:16:26Z","timestamp":1787940986080,"version":"build-2784847793"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20321"],"award-info":[{"award-number":["U23A20321"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62272490"],"award-info":[{"award-number":["62272490"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hunan Province of China","doi-asserted-by":"crossref","award":["2025JJ20062"],"award-info":[{"award-number":["2025JJ20062"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>To enable real-world protein-ligand affinity prediction, not only out-of-distribution generalization but also robustness to variable structural availability and quality should be considered in model design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We present AlignNet, a hierarchical representation alignment framework that mitigates intra- and inter-molecular heterogeneity to learn robust protein-ligand embeddings for generalizable affinity prediction, even from sequence-level inputs. Its intra-molecular module projects unimodal and multimodal features into a unified space, aligning augmented multimodal views for feature fusion and unimodal with multimodal embeddings to distill multimodal priors for structure-agnostic inference. Its inter-molecular module aligns protein and ligand embeddings for cross-molecular integration. Extensive experiments show that AlignNet (i) achieves highly competitive performance, with up to a 20.4% gain in SCC on the challenging LBA 30% split under sequence-only settings, suggesting improved out-of-distribution generalization; and (ii) learns well-separated affinity-related clusters, supporting reliable structure-independent prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>AlignNet is available at https:\/\/github.com\/altriavin\/AlignNet.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag599","type":"journal-article","created":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T11:35:17Z","timestamp":1786275317000},"source":"Crossref","is-referenced-by-count":0,"title":["Structure-agnostic protein\u2013ligand binding affinity prediction via hierarchical representation alignment"],"prefix":"10.1093","volume":"42","author":[{"given":"Xiaowen","family":"Hu","sequence":"first","affiliation":[{"name":"School of Computer Science and Engineering, Central South University , Changsha 410083,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Electrical Engineering & Robotics, Queensland University of Technology , Brisbane, QLD 4000,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering, Central South University , Changsha 410083,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering, Central South University , Changsha 410083,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenggang","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University , Changsha 410078,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering, Central South University , Changsha 410083,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0977-3600","authenticated-orcid":false,"given":"Min","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute for Infocomm Research, Agency for Science, Technology and Research (A*STAR) , Singapore 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