{
  "abstract": "Designing RNA sequences that fold into predefined 3D structures is central to RNA engineering, yet it remains challenging due to the scarcity of experimentally determined structures and the complex sequence-structure relationships. Here, we present RiboDFM, a backbone-conditioned discrete flow-matching framework for RNA sequence design. RiboDFM progressively resolves fully masked sequences by integrating a geometric backbone encoder, an auxiliary base-pairing prediction head, and language model representations into a discrete flow sampler. To expand our training data, we supplemented experimental structures with a large-scale collection of trRosettaRNA2-predicted models. Across diverse benchmarks, RiboDFM achieves high sequence recovery and generates sequences with greater tertiary-structure self-consistency than existing methods. RiboDFM also performs strongly on aptamer-focused design tasks. Finally, beyond sequence generation, the nucleotide probabilities derived from RiboDFM' s flow trajectory serve as an intrinsic measure of sequence-structure compatibility. This enables reliable confidence estimation for designed sequences, as well as reference-free, zero-shot assessment of predicted structure models. Together, these results establish RiboDFM as an effective framework for structure-based RNA sequence design.",
  "abstract_shown": true,
  "affiliations": [
    "Shandong University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "X. Liu"
    },
    {
      "name": "X. An"
    },
    {
      "name": "Z. Peng"
    },
    {
      "name": "W. Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bntq2n0y91me2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.761295",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761295v1.full",
  "id": "bntq2n0y91me2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761295v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "1312|RNA and protein synthesis mechanisms"
    ]
  ],
  "openalex": "W7223448713",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761295v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bntq2n0y91me2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:24Z",
      "native_id": "10.64898/2026.10.22.761295",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761295v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "RiboDFM: Robust RNA sequence design using backbone-conditioned discrete flow matching",
  "title_text": "RiboDFM: Robust RNA sequence design using backbone-conditioned discrete flow matching",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:24Z",
  "url": "https://research.draconitic.com/paper/bntq2n0y91me2",
  "venue": "bioRxiv",
  "versions": []
}