{
  "abstract": "Designing RNA sequences that reliably adopt functional three-dimensional structures remains a central challenge in RNA engineering because folding depends on cooperative interactions beyond canonical base pairing. Here we present DS3dRNA, an interaction-based framework for de novo RNA sequence design that combines a three-body statistical potential with physics-guided sequence sampling and supports design against multiple conformations. Across the evaluated benchmarks, DS3dRNA outperformed representative RNA inverse-design methods in native-sequence recovery and agreement between predicted and target structures. Energy-sequence-quality analyses further showed that lower design energies generally accompanied higher sequence recovery and macro-averaged F1 scores (MacroF1). Experimentally tested Mango II designs retained high-affinity fluorogenic activity, and five twister ribozyme designs yielded mean endpoint cleavage fractions of 37.7-50.6%, compared with 23.5% for the wild type. These results establish explicit higher-order interaction scoring as a complementary approach to emerging data-driven RNA design methods and provide a framework for designing functional RNAs from experimental or predicted structural ensembles.",
  "abstract_shown": true,
  "affiliations": [
    "Wuhan University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "T. Yuan"
    },
    {
      "name": "D. Wang"
    },
    {
      "name": "X.-L. Chen"
    },
    {
      "name": "H.-L. Tao"
    },
    {
      "name": "C.-C. Z. Zheng"
    },
    {
      "name": "X.-C. Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Y.-L. Tan"
    },
    {
      "name": "X.-H. Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Z.-J. Tan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/54mp8sy46f44m.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.26.754601",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.26.754601v1.full",
  "id": "54mp8sy46f44m",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.26.754601v1",
  "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|RNA and protein synthesis mechanisms"
    ]
  ],
  "openalex": "W7214472556",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.26.754601v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/54mp8sy46f44m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:41Z",
      "native_id": "10.64898/2026.09.26.754601",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.26.754601v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "De novo design of functional RNAs through higher-order interactions",
  "title_text": "De novo design of functional RNAs through higher-order interactions",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:41Z",
  "url": "https://research.draconitic.com/paper/54mp8sy46f44m",
  "venue": "bioRxiv",
  "versions": []
}