{
  "abstract": "The protein folding problem remains a fundamental challenge in biophysics. While energy landscape theory resolves Levinthal's paradox through funnel-shaped landscapes, the quantitative effects of landscape ruggedness on folding kinetics are not fully understood. We introduce a computational model inspired by Gömböc, a convex 3D shape with one stable equilibrium and one unstable equilibrium, as an analogy for protein folding landscapes. Using a tunable ruggedness parameter, we simulate “folding” across multiple ruggedness conditions (r = 0 and r = 10−8 to 10−3), spanning five orders of magnitude in the positive-r regime. At minimal ruggedness (10−8), the model achieves 83% success in reaching native-like states. Increasing the ruggedness to 10−7–10−5 reduces the success rate to 25–39%, reflecting landscape trapping as an analog for kinetic trapping in physical folding. Benchmarking against the TPR1 domain via Rosetta and AlphaFold3 reveals native-like coverages of 77% and 90%, respectively, showing qualitative correspondence with the Gömböc model's success rates at low ruggedness. These findings suggest that the Gömböc-inspired model captures essential features of folding landscape quality and may serve as a useful heuristic for comparing foldability across different systems, bridging mathematical topology with protein biophysics.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Chemoinformatics, Infochemistry Scientific Center, ITMO University Lomonosova Street 9 Saint Petersburg 191002 Russia",
    "Department of Biology and General Genetics, Sechenov First Moscow State Medical University (Sechenov University) Izmaylovskiy Boulevard 8 Moscow 105043 Russia",
    "College of Engineering and Applied Science, University of Wisconsin-Milwaukee Milwaukee WI 53211 USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sergey Shityakov",
      "orcid": "0000-0002-6953-9771"
    },
    {
      "affs": [
        0
      ],
      "name": "Ekaterina V. Skorb",
      "orcid": "0000-0003-0888-1693"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Michael Nosonovsky",
      "orcid": "0000-0003-0980-3670"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6r99rj5xf75mj.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra07903b",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733664/",
  "id": "6r99rj5xf75mj",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://doi.org/10.1039/d6ra07903b",
  "language": "en",
  "licence": "CC-BY-NC-3.0",
  "licence_label": "CC BY-NC 3.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/3.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7225254443",
  "pdf_url": "https://pubs.rsc.org/ra/article-pdf/doi/10.1039/d6ra07903b/15033433/d6ra07903b.pdf",
  "pmcid": "PMC13733664",
  "pmid": "42985218",
  "published": "2026-11-04",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/6r99rj5xf75mj.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:23Z",
      "native_id": "PMC13733664",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6ra07903b"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "When does a funnel become a trap? A Gömböc-inspired model of protein folding landscapes",
  "title_text": "When does a funnel become a trap? A Gömböc-inspired model of protein folding landscapes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:23Z",
  "url": "https://research.draconitic.com/paper/6r99rj5xf75mj",
  "venue": "RSC Advances",
  "versions": []
}