{
  "abstract": "Transition state (TS) generation is typically evaluated by geometric similarity, yet low root-mean-square deviation (RMSD) does not establish first-order saddle-point character or reaction-path connectivity. Here we introduce Kairos-GFM, a deterministic equivariant flow-matching model that combines a two-dimensional reaction graph with the Kabsch-aligned mean of three-dimensional reactant and product geometries. Using 881 Transition1x reactions whose reference TSs passed strict saddle-point and bidirectional intrinsic reaction coordinate validation, Kairos-GFM generates one candidate in 0.0118 s with a median RMSD of 0.14 [A]. A hierarchical physical-validation framework--spanning reaction-center geometry, raw single-point energy, DFT saddle-point optimization, harmonic frequency analysis, and IRC endpoint matching reveals that low RMSD and saddle-point convergence do not guarantee the intended reaction channel. Kairos-GFM recovers the target channel in 75.94% of reactions, outperforming diffusion-based baselines but remaining below transport-based methods. These results position Kairos-GFM as a rapid initial-geometry generator for quantum-chemical refinement and provide a transferable validation standard that distinguishes geometric similarity from physical fidelity.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Ministry of Education; School of Pharmacy, Shihezi University, Shihezi 832002, China"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "h. Li"
    },
    {
      "name": "S. Yu"
    },
    {
      "name": "Q. Zhu"
    },
    {
      "name": "Z. Liu"
    },
    {
      "name": "Y. Li"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ba5rwbe2cpz2a.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.30.755629",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755629v1.full",
  "id": "ba5rwbe2cpz2a",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755629v1",
  "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",
      "biochemistry"
    ],
    [
      "openalex",
      "3107|Advanced Chemical Physics Studies"
    ]
  ],
  "openalex": "W7215080805",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755629v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ba5rwbe2cpz2a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:39Z",
      "native_id": "10.64898/2026.09.30.755629",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755629v1"
    }
  ],
  "subjects": [
    {
      "field": "physics",
      "origin": "openalex:3107|Advanced Chemical Physics Studies",
      "subfield": "amo"
    }
  ],
  "title": "Beyond RMSD: Deterministic Dlow Matching for Ultrafast and Physically Validated Transition-State Generation",
  "title_text": "Beyond RMSD: Deterministic Dlow Matching for Ultrafast and Physically Validated Transition-State Generation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:39Z",
  "url": "https://research.draconitic.com/paper/ba5rwbe2cpz2a",
  "venue": "bioRxiv",
  "versions": []
}