{
  "abstract": "Small-molecule drugs often act by stabilizing specific protein conformations, yet most biophysical screening platforms report binding affinity or kinetics without directly capturing structural response. Here we introduce molecular friction sensing (MFS), a screening-compatible approach that detects ligand-induced changes in protein conformation through changes in hydrodynamic drag exerted on electrically switchable DNA origami nanolevers. Across a diverse protein panel and under physiological conditions, the method quantitatively reports protein size and resolves ligand-dependent conformational shifts with sub-Angström sensitivity. In maltodextrin-binding protein, cognate and non-cognate maltodextrins produced distinct friction signatures that mirrored their biological roles. In a carbonic anhydrase screen, molecular friction sensing identified compound-dependent conformational responses among SPR-validated binders, revealing that affinity and kinetics do not predict structural outcome. Molecular friction sensing therefore adds a structural dimension to interaction analysis and provides a route to prioritize drug candidates by the conformations they induce.",
  "abstract_shown": true,
  "affiliations": [
    "Bruker Dynamic Biosensors, Bruker Daltonics GmbH & Co. KG, Perchtinger Str. 8/10, Munich, Germany, 81379",
    "Kurt-Schwabe-Institut für Mess- und Sensortechnik Meinsberg e.V.",
    "Technical University Darmstadt, Karolinenplatz 5, Darmstadt, Germany, 64289",
    "Ludwig-Maximilians-Universität München, Butenandtstr. 5–13, Munich, Germany, 81377",
    "Technical University Dresden"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Pablo Porragas Paseiro",
      "orcid": "0009-0007-4422-5593"
    },
    {
      "affs": [
        0
      ],
      "name": "Lukas Aufinger",
      "orcid": "0000-0001-9573-2738"
    },
    {
      "affs": [
        1
      ],
      "name": "Alfred Kick"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Tereza Jahodová"
    },
    {
      "affs": [
        0
      ],
      "name": "Veronica Hamer"
    },
    {
      "affs": [
        0,
        1,
        4
      ],
      "name": "Ulrich Rant",
      "orcid": "0000-0002-6100-828X"
    },
    {
      "affs": [
        0
      ],
      "name": "Wouter Engelen",
      "orcid": "0000-0001-8779-9887"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/df798bnpf20s2.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15004867/v2",
  "fulltext_url": null,
  "id": "df798bnpf20s2",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15004867/v2",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Advanced biosensing and bioanalysis techniques"
    ]
  ],
  "openalex": "W7214807761",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15004867/v2",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-29",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/df798bnpf20s2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "10.26434/chemrxiv.15004867",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15004867/v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Advanced biosensing and bioanalysis techniques",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Screening Protein Conformational Responses by Molecular Friction Sensing",
  "title_text": "Screening Protein Conformational Responses by Molecular Friction Sensing",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/df798bnpf20s2",
  "venue": "ChemRxiv",
  "versions": []
}