{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:39:46Z","timestamp":1792449586074,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":278,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001230","name":"Macquarie University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Insect odorant receptors (iORs) essential for olfaction function as 7-transmembrane-domain (7TM) ion channels. iORs form tetrameric complexes that include a highly conserved odorant receptor co-receptor (Orco). Functional Orco homotetramers have also known to form ex vivo. Blocking Orco ex vivo and in vivo disrupts olfactory signalling, making it a promising target for functional intervention. Understanding its gating behaviour is critical for developing strategies to disrupt odour-guided behaviours in disease-vector insects. Thus, insights into the dynamic gating of the Anopheles gambiae Orco have implications on the rational design of vector-control strategies against malaria. We studied molecular dynamics (MD) simulations on homotetrameric AgamOrco models generated using template-based modelling (TBM) and AlphaFold3 (AF3), to investigate ligand-dependent pore dynamics. Agonist and antagonist bound systems were analysed to understand the ligand-dependent gating.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results show that apo and antagonistic IPC-bound AgamOrco homotetramer models remain in a stable, closed, and non-conductive state across both models. TBM, but not AF3, successfully captures agonistic VUAA1-induced activation, consistent with experimental observations, exhibiting asymmetric pore widening and conformational changes. Antagonist displacement simulations confirm IPC-mediated pore closure. Overall, the TBM AgamOrco model provides a reliable framework for structure-guided discovery of novel agents for control of insect pests and vector diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioadv\/vbag295","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:22:15Z","timestamp":1791199335000},"source":"Crossref","is-referenced-by-count":0,"title":["Decoding channel pore dynamics mechanism in\n                    <i>Anopheles gambiae<\/i>\n                    Orco homotetramer"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9990-2773","authenticated-orcid":false,"given":"Vaanathi","family":"Chidambara Thanu","sequence":"first","affiliation":[{"name":"Applied BioSciences, Macquarie University , Sydney, NSW 2109,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7606-0195","authenticated-orcid":false,"given":"Amara","family":"Jabeen","sequence":"additional","affiliation":[{"name":"Applied BioSciences, Macquarie University , Sydney, NSW 2109,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6580-7150","authenticated-orcid":false,"given":"Georgia","family":"Kythreoti","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences - Deree, The American College , Athens 15342,","place":["Greece"]},{"name":"Institute of Biosciences & Applications, National Centre for Scientific Research \u201cDemokritos\u201d , Athens 15341,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-4138","authenticated-orcid":false,"given":"Kostas","family":"Iatrou","sequence":"additional","affiliation":[{"name":"Institute of Biosciences & Applications, National Centre for Scientific Research \u201cDemokritos\u201d , Athens 15341,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8455-2352","authenticated-orcid":false,"given":"Spyros E","family":"Zographos","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology, National Hellenic Research Foundation , Athens 11635,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7574-7737","authenticated-orcid":false,"given":"Philip W","family":"Taylor","sequence":"additional","affiliation":[{"name":"Applied BioSciences, Macquarie University , Sydney, NSW 2109,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8290-813X","authenticated-orcid":false,"given":"Shoba","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Applied BioSciences, Macquarie University , Sydney, NSW 2109,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"2026101917515035400_vbag295-B1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"2026101917515035400_vbag295-B2","doi-asserted-by":"publisher","first-page":"W547","DOI":"10.1093\/nar\/gkaf394","article-title":"The UniProt website API: facilitating programmatic access to protein knowledge","volume":"53","author":"Ahmad","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"2026101917515035400_vbag295-B3","doi-asserted-by":"publisher","first-page":"100172","DOI":"10.1016\/j.crpvbd.2024.100172","article-title":"Is Anopheles gambiae (sensu stricto), the principal malaria vector in Africa prone to resistance development against new insecticides? 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