{
  "abstract": "Per- and polyfluoroalkyl substances (PFAS) are persistent anthropogenic \"forever chemicals\" whose strong C-F bonds (~460-533 kJ mol-1) resist defluorination, and the recast EU Drinking Water Directive sets parametric values of 0.10 ug L-1 for the sum of 20 specified PFAS and 0.50 ug L-1 for total PFAS. Here, we present DeFluorX, a mechanism-first pipeline that uses Boltz-2 to co-fold 2,150 bacterial fluoroacetate dehalogenase (FAcD) variants with 26 PFAS and fluoroacetate, generating uniformly high model confidence (rho = +0.08) but poorly tracked catalytic competence. Thus, the complexes were ranked and tiered by SN2-defluorination geometry based on the known mechanism of control of FAcDs RPA1163 with fluoroacetate: Odelta...C-alpha distance and Odelta-C-alpha-F angle; relay; carboxylate clamp; F-stabiliser; F-cradle; and penalties for scissile bond strength, backside occlusion, beta-fluorination and bond multiplicity. The tiering identified eight complexes (med angle 173.2 degrees, distance 2.91 A) with a high probability of degradation, including Alphaproteobacterial enzymes, with mono-, di- and trifluoroacetate attacking at 172-178 degrees versus 163 degrees for the control. We performed WaterMap, restrained 1 us Desmond MD, MM-GBSA and scans of the three WaterMap-aware best MD frames per complex using B3LYP/6-31G** QM/MM. All 12 frames exhibited product-end C-F cleavage with barriers ranging from 1.1 to 11.8 kcal mol-1, and the departing fluoride carried -0.43 to -0.63 e. The Laboratory validation is ongoing.",
  "abstract_shown": true,
  "affiliations": [
    "Section of Plant Glycobiology, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C-1871, Denmark."
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "S. Ahmad"
    },
    {
      "name": "A. Forouzandeh"
    },
    {
      "name": "B. Togni"
    },
    {
      "name": "J. B. Randloev"
    },
    {
      "name": "M. Ogden"
    },
    {
      "affs": [
        0
      ],
      "name": "T. K. Nielsen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/16fe218frecar.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.11.758284",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758284v1.full",
  "id": "16fe218frecar",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758284v1",
  "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",
      "bioinformatics"
    ],
    [
      "openalex",
      "2304|Per- and polyfluoroalkyl substances research"
    ]
  ],
  "openalex": "W7221448116",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758284v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/16fe218frecar.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:17Z",
      "native_id": "10.64898/2026.10.11.758284",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758284v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Mechanism-guided Discovery of Fluoroacetate Dehalogenase (FAcD) Variants for Enzymatic PFAS Defluorination",
  "title_text": "Mechanism-guided Discovery of Fluoroacetate Dehalogenase (FAcD) Variants for Enzymatic PFAS Defluorination",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:25Z",
  "url": "https://research.draconitic.com/paper/16fe218frecar",
  "venue": "bioRxiv",
  "versions": []
}