{
  "abstract": "Motivation\n\nAntibody-antigen (Ab-Ag) interactions are central to immune recognition and widely exploited in therapeutic design, making accurate structural characterization of these complexes a central challenge in the field. While docking and artificial intelligence-based approaches can generate multiple candidate binding modes, reliably identifying near-native conformations represent a key bottleneck. Existing methods depend largely on static scoring functions, which fail to capture the dynamic nature of Ab-Ag interfaces and, as a result, offer limited power to discriminate between competing poses.Results\n\nHere, we evaluate heated molecular dynamics (HMD) as a strategy to discriminate binding pose quality based on structural stability under thermal perturbation, implemented through the automated workflow AutoHMD. Across a diverse set of Ab-Ag complexes, HMD enabled clear separation between high-quality and incorrect poses. During simulations, near-native complexes maintained a stable interface, whereas incorrect ones showed progressive divergence, particularly at elevated temperatures. Interaction analysis revealed that high-quality poses maintain more stable and persistent interfacial contacts throughout the simulations. In contrast, incorrect poses display an unstable interaction network. Additional simulation replicates increased classification consistency, while a mean iRMSD cutoff of approximately 2.5 Å achieved 90% accuracy in cross-validation and retained robust performance on an independent external set. Its transfer to Boltz-2-generated complexes further supported the broader applicability of HMD to AI-predicted binding poses. Overall, AutoHMD provides a reproducible, scalable, and high-throughput framework for validation of predicted antibody-antigen complexes, with potential applications in structural bioinformatics and biopharmaceutical design.",
  "abstract_shown": true,
  "affiliations": [
    "Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, Av. Humberto Monte s/n, Fortaleza, Ceará, 60020-181, Brazil.",
    "Structural and Functional Biology in Biopharmaceuticals Group, Fiocruz Ceará, R. São José, s/n, Eusébio, Ceará, 61773-270, Brazil.",
    "Postgraduate Program in Computational and Systems Biology, Oswaldo Cruz Foundation (Fiocruz), Av. Brasil, 4365, Rio de Janeiro, Rio de Janeiro, 21040-900, Brazil.",
    "Pasteur-Fiocruz Center on Immunology and Immunotherapy, Oswaldo Cruz Foundation (Fiocruz), R. São José, S/N, Eusébio, Ceará, 61773-270, Brazil."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Julia S Souza",
      "orcid": "0009-0002-5113-7595"
    },
    {
      "affs": [
        1
      ],
      "name": "Aline O Albuquerque",
      "orcid": "0000-0003-2072-157X"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Diego S Almeida",
      "orcid": "0009-0006-5320-1596"
    },
    {
      "affs": [
        1
      ],
      "name": "Andrielly H S Costa",
      "orcid": "0000-0002-5871-8352"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jean V Sampaio",
      "orcid": "0009-0004-7717-5076"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "João H M Silva",
      "orcid": "0000-0003-1534-9857"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ceh5c3p3kb8qc.bib",
  "cited_by": 0,
  "doi": "10.1093/bioinformatics/btag757",
  "fulltext_url": "https://europepmc.org/articles/PMC13693361",
  "id": "ceh5c3p3kb8qc",
  "issns": [
    "1367-4803",
    "1367-4811"
  ],
  "landing_url": "https://europepmc.org/article/MED/42853673",
  "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|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7221080637",
  "pdf_url": "https://europepmc.org/articles/PMC13693361?pdf=render",
  "pmcid": "PMC13693361",
  "pmid": "42853673",
  "published": "2026-10-01",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/ceh5c3p3kb8qc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:12Z",
      "native_id": "MED:42853673",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42853673"
    },
    {
      "first_seen": "2026-10-30T12:19:38Z",
      "native_id": "10.1093/bioinformatics/btag757",
      "source": "crossref",
      "url": "https://academic.oup.com/bioinformatics/article/doi/10.1093/bioinformatics/btag757/8898726"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "AutoHMD: scalable and accurate validation of antibody-antigen complexes by heated molecular dynamics.",
  "title_text": "AutoHMD: scalable and accurate validation of antibody-antigen complexes by heated molecular dynamics.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:38Z",
  "url": "https://research.draconitic.com/paper/ceh5c3p3kb8qc",
  "venue": "Bioinformatics (Oxford, England)",
  "versions": []
}