{
  "abstract": "RNA-DNA hybridization is relevant to several molecular processes, but computational energy estimates alone cannot establish hybrid formation in cells. This study presents a computational framework for comparing model-derived RNA-DNA and DNA-DNA energy metrics across 16 selected regions of the HIV-1 reference genome HXB2 (GenBank accession K03455.1). The operational metric was defined as the difference between the RNA-DNA calculation and the DNA-DNA reference calculation (ΔΔG_model). Across the 16 regions, 15 yielded negative metric values and one yielded a positive value. The mean was −8.00 kcal/mol (sample standard deviation, 5.45 kcal/mol). A two-sided one-sample t-test against zero gave t(15) = −5.87, p = 3.08 × 10⁻⁵. The mean remained negative in sensitivity analyses excluding either or both of the overlapping TAR and R5LTR regions. These findings describe a consistent direction in the selected computational panel. However, the regions are drawn from a single reference genome, are not independent biological replicates, and may not represent independent sequence information. Furthermore, our independent verification confirmed that while the RNA-DNA energies are highly reproducible, the DNA-DNA reference energy is highly dependent on the specific algorithmic approach. Eleven of the 16 DNA-DNA reference values showed numerical agreement with standard DuplexFold calculations, while five regions showed discrepancies (1.1–5.3 kcal/mol) that remain unresolved. The results do not demonstrate intracellular RNA-DNA hybrid formation or genomic R-loop formation. Instead, they provide a testable computational hypothesis for further evaluation through reproducible energy calculations and independent experimental measurements.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Research in Fundamental Sciences"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Saadat Samadi",
      "orcid": "0009-0008-2861-7471"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7xza5xm3zn7dw.bib",
  "cited_by": 0,
  "doi": "10.5281/zenodo.23615302",
  "fulltext_url": null,
  "id": "7xza5xm3zn7dw",
  "issns": [],
  "landing_url": "https://zenodo.org/records/23615302",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": "https://zenodo.org/api/records/23615302/files/HIV1_thermodynamic_framework_full_v1.pdf/content",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7xza5xm3zn7dw.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:20:56Z",
      "native_id": "23615302",
      "source": "zenodo",
      "url": "https://zenodo.org/records/23615302"
    }
  ],
  "subjects": [],
  "title": "A General Computational Framework for Sequence-Level Thermodynamic Analysis of Modeled RNA-DNA and DNA-DNA Duplex States: A Proof-of-Concept Study in HIV-1",
  "title_text": "A General Computational Framework for Sequence-Level Thermodynamic Analysis of Modeled RNA-DNA and DNA-DNA Duplex States: A Proof-of-Concept Study in HIV-1",
  "type": "preprint",
  "updated_at": "2026-11-07T12:20:56Z",
  "url": "https://research.draconitic.com/paper/7xza5xm3zn7dw",
  "venue": "Zenodo",
  "versions": []
}