{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:48:38Z","timestamp":1782308918009,"version":"3.54.5"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":1,"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":["62171251"],"award-info":[{"award-number":["62171251"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Structure-based drug design (SBDD) aims to generate ligand molecules that tightly bind to specific protein targets, a critical step in drug discovery. Diffusion models have shown promise for this task, yet existing methods struggle to effectively incorporate protein\u2013ligand interaction priors during generation. Most approaches rely on protein-specific structural priors that remain fixed throughout generation, limiting molecular diversity and failing to capture the dynamic interplay between protein pockets and ligand atoms, which is essential for achieving high binding affinity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We propose DPDiff, a disentangled prior-conditioned diffusion model for protein-specific 3D molecular generation. DPDiff introduces two complementary interaction prior networks that capture geometry-based spatial interactions and sequence-based interactions robust to structural noise. During generation, the model dynamically extracts interaction priors using intermediate diffusion predictions and adaptively fuses them via a time-dependent adapter. A disentangled denoising network balances prior guidance with generative flexibility. Experiments on the CrossDocked2020 dataset demonstrate that DPDiff generates molecules with more realistic 3D structures and state-of-the-art binding affinities, achieving an average Vina Dock score of \u22128.58 and a high affinity ratio of 69.4%, outperforming existing methods while maintaining favorable drug-likeness and synthetic accessibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The source code of DPDiff is available at https:\/\/github.com\/ZerinHwang03\/DPDiff.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag165","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T12:23:33Z","timestamp":1777638213000},"source":"Crossref","is-referenced-by-count":0,"title":["Disentangled diffusion model for 3D molecular generation with protein\u2013ligand interaction 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510700,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Xing","sequence":"additional","affiliation":[{"name":"Institute of Perceptual Intelligence, Peng Cheng Laboratory , Shenzhen, 518000,","place":["China"]},{"name":"China Southern Power Dispatching and Control Center, China Southern Power Grid , Guangzhou, 510700,","place":["China"]},{"name":"Institute of Computing, University of Chinese Academy of Sciences , Beijing, 100080,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Perceptual Intelligence, Peng Cheng Laboratory , Shenzhen, 518000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Computing, University of Chinese Academy of Sciences , Beijing, 100080,","place":["China"]},{"name":"School of Artificial Intelligence, University of Chinese Academy of Sciences , Beijing, 100080,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shenzhen International Graduate School, Tsinghua University , Shenzhen, 518000,","place":["China"]},{"name":"Department of Network Intelligence, Pengcheng Laboratory , Shenzhen, 518000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Network Intelligence, Pengcheng Laboratory , Shenzhen, 518000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7108-3574","authenticated-orcid":false,"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"Computer Science Program, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah 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