{
  "abstract": "Background: 2-Amino-9H-pyrido[2,3-b]indole (AαC) is a mutagenic and carcinogenic heterocyclic aromatic amine formed by pyrolysis of proteins in cooked meat and present in tobacco smoke. After metabolic activation to a reactive nitrenium ion, it modifies DNA covalently, mainly at guanine. How AαC first associates with DNA, before any covalent bond forms, is not well understood. Methods: We docked AαC to three B-DNA dodecamers (PDB IDs 1BNA, 2Z2G and 2HKC) with PatchDock and FireDock, and ran explicit-solvent molecular dynamics (MD) simulations of the docked complexes in NAMD 2.13 with the CHARMM36 force field (1BNA: 10 ns; 2Z2G: 50 ns; NPT, 300 K, 0.15 M NaCl). Results: AαC bound in the minor groove of all three dodecamers, with global binding energies of -50.08 (1BNA), -53.41 (2Z2G) and -45.22 kcal/mol (2HKC). Atomic van der Waals terms contributed -16.41 to -18.36 kcal/mol, and single hydrogen bonds to thymine, guanine or adenine oxygen atoms were identified (2.2–2.8 Å). In the simulations AαC remained bound with a low, stable backbone RMSD, whereas the DNA backbone fluctuated considerably more. The minor-groove poses were poorly oriented for covalent attack when the base pairs were intact and canonical. Conclusions: Neutral AαC forms stable, groove-bound non-covalent complexes with B-DNA, but these complexes do not by themselves position the amine for C8-guanine adduct formation. Local distortion of the DNA, or the charged nitrenium ion, may be required. The complexes presented here serve as starting structures for ongoing quantum-mechanical studies of nitrenium ion stability and covalent adduct formation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "Gurudeeban Selvaraj",
      "orcid": "0000-0002-7223-3853"
    },
    {
      "name": "Satyavani Kaliamurthi"
    },
    {
      "name": "Gilles H. Peslherbe"
    },
    {
      "name": "Dong-qing Wei"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/78wx8fn0c7fnr.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010963/v1",
  "fulltext_url": null,
  "id": "78wx8fn0c7fnr",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010963/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Carcinogens and Genotoxicity Assessment"
    ]
  ],
  "openalex": "W7223400949",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010963/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/78wx8fn0c7fnr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:26Z",
      "native_id": "10.26434/chemrxiv.15010963",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010963/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Carcinogens and Genotoxicity Assessment",
      "subfield": "oncology"
    }
  ],
  "title": "Binding Mode of the Heterocyclic Amine 2-Amino-9H-pyrido[2,3-b] indole (AαC) to DNA Elucidated by Molecular Docking and Molecular Dynamics Simulation",
  "title_text": "Binding Mode of the Heterocyclic Amine 2-Amino-9H-pyrido[2,3-b] indole (AαC) to DNA Elucidated by Molecular Docking and Molecular Dynamics Simulation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:26Z",
  "url": "https://research.draconitic.com/paper/78wx8fn0c7fnr",
  "venue": "ChemRxiv",
  "versions": []
}