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On the account of AR being a \u201cpotentially attractive immunological target\u201d, an immunoinformatics pipeline was built to identify and screen mutation\u2010independent, broad MHC covering, potential antigenic, non\u2010allergenic, non\u2010toxic and soluble epitopes. The filtered epitopes required assembly into a unified construct with interconnecting linkers and adjuvant and further TLR3\u2010docking. We chose TLR3 because of its pro\u2010apoptotic activity in prostate cancer, to check active immune response by the vaccine. Our study was not confined to the use of a conventional adjuvant like human beta defensin\u20103 but it extended to the scope of utilization of a protein\u2010based TLR3\u2010specific agonist as an adjuvant for assembling the second composite construct. Our path was guided by the discovery of TLR3\u2010specific agonist minibinder 8.6 (a small, hyperstable protein) by Adams et\u00a0al. An extensively comparative molecular dynamics study of the free state and bound states of the two constructs unveiled a more stable interaction, complex stability and immune response attributing to the specificity of the minibinder\u2010based construct towards TLR3. Our work circumscribes a multi\u2010headed approach beginning with peptide subunit multi\u2010epitope vaccine construct design for mitigating mCRPC; secondarily, endorsing the advocacy of TLR3\u2010agonizing minibinders as vaccine adjuvants for enhanced immunity and finally posing a comparative framework of minibinder 8.6 over HBD3, as a more potential adjuvant, apprehending wet\u2010lab proof.<\/jats:p>","DOI":"10.1002\/prot.70124","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T02:24:26Z","timestamp":1771640666000},"page":"1371-1402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Binding Dynamics of Minibinder 8.6 and\n                    <scp>HBD3<\/scp>\n                    With\n                    <scp>TLR3<\/scp>\n                    as Adjuvants for Developing a Peptide\u2010Based Multi\u2010Epitope Subunit Vaccine Against\n                    <scp>mCRPC<\/scp>\n                    : A Molecular Dynamics Study"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6074-9290","authenticated-orcid":false,"given":"Ishani","family":"Paul","sequence":"first","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumyadeep","family":"Ray","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muskan","family":"Tewari","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3603-4593","authenticated-orcid":false,"given":"Mowmita","family":"Saha","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University  Kolkata India"},{"name":"Department of Zoology Seth Anandram Jaipuria College  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7562-6794","authenticated-orcid":false,"given":"Sujay","family":"Ray","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864\u2010024\u201001215\u20102"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17061013"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.5489\/cuaj.8373"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30060432"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.859785"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201018\u20101431"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.100962"},{"issue":"7","key":"e_1_2_11_9_1","first-page":"2892","article-title":"Androgen Receptor Stabilization in Recurrent Prostate Cancer Is Associated With Hypersensitivity to Low Androgen","volume":"61","author":"Gregory C. 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