{
  "abstract": "The sequence-dependent mechanical landscapes of double-stranded nucleic acids (dsNAs) remain largely unexplored beyond canonical dsDNA. We describe cgNA+, a coarse-grained predictive model of the mechanics of dsRNA, DNA:RNA hybrids, and epigenetically modified dsDNA, all parameterised from 1.26 milliseconds of atomistic simulations. cgNA+ predicts non-local sequence-dependent equilibrium shape and stiffness with errors an order of magnitude smaller than sequence-variability, while enabling exploration of numbers/lengths of sequences inaccessible to atomistic simulation. We show that dsNA equilibrium shape is strongly influenced by flanking sequence up to octamer context, with flexible dimer-steps more context-sensitive. CpG-modification alters equilibrium shape comparable to changes caused by single-nucleotide polymorphisms. Groove-width analysis across dsNA decamers reveals strong sequence dependence, reflecting the differing characteristic helical-geometry of dsDNA and dsRNA, whereas DRHs exhibit mixed behaviour depending on DNA-strand pyrimidine content. CTCF binding sites exhibit a distinct groove-width signature. Persistence-length spectra from [~]9 million sequences indicate that dsRNA is stiffer than dsDNA, whereas DRH exhibits intermediate stiffness modulated by DNA-strand pyrimidine content. Persistence length increases upon CpG-modification, but decreases on hypermodification. Overall, the cgNA+ model enables a first, highly accurate (compared to atomistic simulations), very large-scale, comparative study of sequence-dependent mechanics both within and across dsNA classes, demonstrating previously hidden regulatory layers.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Mathematics, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "R. Sharma"
    },
    {
      "name": "A. S. Patelli"
    },
    {
      "name": "R. Singh"
    },
    {
      "name": "D. Petkeviciute-Gerlach"
    },
    {
      "name": "O. Gonzalez"
    },
    {
      "name": "J. H. Maddocks"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5jnp31kvebstn.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.09.740023",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.09.740023v2.full",
  "id": "5jnp31kvebstn",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.09.740023v2",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "1312|DNA and Nucleic Acid Chemistry"
    ]
  ],
  "openalex": "W7202159430",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.09.740023v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5jnp31kvebstn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:28Z",
      "native_id": "10.64898/2026.08.09.740023",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.09.740023v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Sequence-dependent conformational and mechanical landscapes of double-stranded nucleic acids",
  "title_text": "Sequence-dependent conformational and mechanical landscapes of double-stranded nucleic acids",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:28Z",
  "url": "https://research.draconitic.com/paper/5jnp31kvebstn",
  "venue": "bioRxiv",
  "versions": []
}