{
  "abstract": "SARS-CoV-2 nonstructural protein 13 (nsp13) is a highly conserved helicase that couples ATP hydrolysis to RNA translocation through long-range allosteric communication between its ATPase and RNA-binding domains. In prior work, we identified L405 as a key regulator of interdomain motions and proposed that the L405D mutation would disrupt this coupling by perturbing conformational transitions required for translocation [J. Phys. Chem. B2024, v128, 492-503. ]. Subsequent experiments confirmed that L405D attenuates helicase activity and ATPase activity, implicating the potential formation of a new salt bridge, D405-R560, for both effects [ J. Biol. Chem.2026, v302, 111198.]. Here, we provide a data-driven explanation for both effects by combining Gaussian accelerated molecular dynamics (GaMD) simulations with Shape-GMM clustering and linear discriminant analysis. Whereas wild-type nsp13 exhibits both conformational selection and induction, L405D collapses the conformational landscape to operate predominantly through selection, with ATP-induced structural transitions observed in the wild-type ensemble no longer sampled by the mutant. This loss of induction likely impairs ATP turnover while simultaneously disrupting coordinated motif-RNA interactions required for inchworm translocation. These findings demonstrate how mutation-induced reshaping of conformational ensembles can modulate access to reaction-competent states, providing a general framework for understanding how targeted mutations disrupt catalytic function through allosteric ensemble remodeling in motor proteins.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma74078, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Elham Fazelpour",
      "orcid": "0009-0009-0307-1609"
    },
    {
      "affs": [
        0
      ],
      "name": "Priti Roy"
    },
    {
      "affs": [
        0
      ],
      "name": "Kole J Frederick"
    },
    {
      "affs": [
        0
      ],
      "name": "Martin McCullagh",
      "orcid": "0000-0002-8603-4388"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1nfcxkbz6p6gz.bib",
  "cited_by": 0,
  "doi": "10.1021/acs.jpcb.6c03935",
  "fulltext_url": "https://europepmc.org/articles/PMC13618043",
  "id": "1nfcxkbz6p6gz",
  "issns": [
    "1520-6106",
    "1520-5207"
  ],
  "landing_url": "https://europepmc.org/article/MED/42917542",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7211985961",
  "pdf_url": "https://europepmc.org/articles/PMC13618043?pdf=render",
  "pmcid": "PMC13618043",
  "pmid": "42917542",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1nfcxkbz6p6gz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42917542",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42917542"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Mechanochemical Decoupling of ATP Hydrolysis and RNA Translocation in SARS-CoV-2 nsp13 by the L405D Mutation.",
  "title_text": "Mechanochemical Decoupling of ATP Hydrolysis and RNA Translocation in SARS-CoV-2 nsp13 by the L405D Mutation.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/1nfcxkbz6p6gz",
  "venue": "The journal of physical chemistry. B",
  "versions": []
}