{
  "abstract": "Ion-pairs are central charged motifs that control the biological function of several proteins. Yet, the physical principles linked to the formation of ion-pairs during protein folding remain poorly understood. Here, we show that buried ion-pairs of de novo-designed helical bundle proteins reshape the folding pathways by introducing kinetic barriers that are overcome by a hydrophobic collapse linked to packing of the protein core. By combining protein design with co-translational folding studies, nuclear magnetic resonance (NMR) spectroscopy, and molecular dynamics simulations, we show that introduction of a buried ion-pair leads to a shifted folding transition that balances desolvation and electrostatic interactions within the protein and the bulk solvent. Moreover, we find that the folding pathway is sensitive to modifications in non-polar interactions and motifs that electrostatically shield the ion-pair from its surroundings. Our combined findings provide a blueprint for understanding how functional motifs affect protein folding and how mutation of charged networks alter the stability of proteins.",
  "abstract_shown": true,
  "affiliations": [
    "Stockholm University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "J. Liebau"
    },
    {
      "name": "G. Kemp"
    },
    {
      "name": "D. Auman"
    },
    {
      "name": "N. Hoja"
    },
    {
      "name": "A. Jussupow"
    },
    {
      "name": "M. Baumgart"
    },
    {
      "name": "G. von Heijne"
    },
    {
      "affs": [
        0
      ],
      "name": "V. R. I. Kaila"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9svwc5qv30hzb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.10.757878",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.757878v1.full",
  "id": "9svwc5qv30hzb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.757878v1",
  "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",
      "biophysics"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7221467111",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.757878v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9svwc5qv30hzb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:02Z",
      "native_id": "10.64898/2026.10.10.757878",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.10.757878v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Buried Ion-Pairs Reshape Folding Pathways of Artificial Proteins",
  "title_text": "Buried Ion-Pairs Reshape Folding Pathways of Artificial Proteins",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:02Z",
  "url": "https://research.draconitic.com/paper/9svwc5qv30hzb",
  "venue": "bioRxiv",
  "versions": []
}