{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:44:20Z","timestamp":1792266260481,"version":"4.4.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["2041439"],"award-info":[{"award-number":["2041439"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]},{"name":"South Australian immunoGENomics Cancer Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Proteolysis-targeting chimeras (PROTACs) enable targeted protein degradation through ternary complex formation with E3 ubiquitin ligase. However, the rational design of PROTACs remains highly challenging due to limited structure\u2013activity relationship data and the vast conformational diversity of linkers. Existing computational approaches can be broadly divided into structure-based ternary modelling methods and fragment-based linker generation models. Although these approaches have advanced PROTAC design, they typically neglect key physicochemical constraints and linker-length control during the generation process, causing the generated PROTACs to lack balanced structural properties required for effective ternary complex formation with drug-like characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>To address these limitations, we propose DesignMaster, a diffusion-based generative framework that explicitly incorporates linker length and physicochemical properties as controllable conditioning signals. DesignMaster employs an E(3)-equivariant graph Transformer with a gated multi-condition fusion module to inject linker length and physicochemical constraints throughout the diffusion process, enabling fine-grained and constraint-aware molecular generation. Experiments on PROTAC-DB 2.0 and 3.0 demonstrate that DesignMaster achieves the best or highly competitive performance across Validity, Uniqueness, and Recovery. The Case study further shows that DesignMaster consistently achieves improved geometric agreement with the reference PROTAC conformations across both the 6W7O and 6HAY complexes, highlighting its potential for practical structure-guided and property-aware PROTAC design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability<\/jats:title>\n                    <jats:p>The source code and datasets are available at https:\/\/github.com\/ABILiLab\/DesignMaster.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag714","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:57:32Z","timestamp":1790164652000},"source":"Crossref","is-referenced-by-count":0,"title":["DesignMaster: a multi-conditional diffusion framework for rational PROTAC design"],"prefix":"10.1093","volume":"42","author":[{"given":"Binze","family":"Shi","sequence":"first","affiliation":[{"name":"School of Computer Science, Northwestern Polytechnical University , Xi\u2019an, Shaanxi 710129,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Hao","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide University , Adelaide, SA 5005,","place":["Australia"]},{"name":"College of Information Engineering, Northwest A&F University , Yangling, Shaanxi 712100,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide University , Adelaide, SA 5005,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Pan","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide University , Adelaide, SA 5005,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Isbel","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide University , Adelaide, SA 5005,","place":["Australia"]},{"name":"Adelaide Centre for Epigenetics (ACE), Adelaide University , Adelaide, SA 5005,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Roy","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide University , Adelaide, SA 5005,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9690-0879","authenticated-orcid":false,"given":"Ashley P","family":"Ng","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research , Parkville, VIC 3050,","place":["Australia"]},{"name":"Sir Peter MacCallum Department of Oncology, The University of Melbourne , Parkville, VIC 3010,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuequn","family":"Shang","sequence":"additional","affiliation":[{"name":"School of Computer Science, Northwestern Polytechnical University , Xi\u2019an, Shaanxi 710129,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5216-3213","authenticated-orcid":false,"given":"Fuyi","family":"Li","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide University , Adelaide, SA 5005,","place":["Australia"]},{"name":"College of Information Engineering, Northwest A&F University , Yangling, Shaanxi 712100,","place":["Australia"]},{"name":"Sir Peter MacCallum Department of Oncology, The University of Melbourne , Parkville, VIC 3010,","place":["Australia"]},{"name":"Department of Microbiology and Immunology, 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