{
  "abstract": "Motivation\n\nInsect 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.Results\n\nOur 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.",
  "abstract_shown": true,
  "affiliations": [
    "Applied BioSciences, Macquarie University, Sydney, NSW 2109, Australia.",
    "Department of Natural Sciences - Deree, The American College, Athens 15342, Greece.",
    "Institute of Biosciences & Applications, National Centre for Scientific Research \"Demokritos\", Athens 15341, Greece.",
    "Institute of Chemical Biology, National Hellenic Research Foundation, Athens 11635, Greece."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Vaanathi Chidambara Thanu",
      "orcid": "0009-0000-9990-2773"
    },
    {
      "affs": [
        0
      ],
      "name": "Amara Jabeen",
      "orcid": "0000-0002-7606-0195"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Georgia Kythreoti",
      "orcid": "0000-0002-6580-7150"
    },
    {
      "affs": [
        2
      ],
      "name": "Kostas Iatrou",
      "orcid": "0000-0002-7587-4138"
    },
    {
      "affs": [
        3
      ],
      "name": "Spyros E Zographos",
      "orcid": "0000-0001-8455-2352"
    },
    {
      "affs": [
        0
      ],
      "name": "Philip W Taylor",
      "orcid": "0000-0002-7574-7737"
    },
    {
      "affs": [
        0
      ],
      "name": "Shoba Ranganathan",
      "orcid": "0000-0002-8290-813X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f560vjhn8td0x.bib",
  "cited_by": 0,
  "doi": "10.1093/bioadv/vbag295",
  "fulltext_url": "https://europepmc.org/articles/PMC13679930",
  "id": "f560vjhn8td0x",
  "issns": [
    "2635-0041"
  ],
  "landing_url": "https://europepmc.org/article/MED/42899295",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7220726625",
  "pdf_url": "https://europepmc.org/articles/PMC13679930?pdf=render",
  "pmcid": "PMC13679930",
  "pmid": "42899295",
  "published": "2026-10-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f560vjhn8td0x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42899295",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42899295"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Decoding channel pore dynamics mechanism in Anopheles gambiae Orco homotetramer.",
  "title_text": "Decoding channel pore dynamics mechanism in Anopheles gambiae Orco homotetramer.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/f560vjhn8td0x",
  "venue": "Bioinformatics advances",
  "versions": []
}