{
  "abstract": "The ability of migratory birds to orient using the Earth’s magnetic field has been proposed to rely on a radical-pair mechanism operating within Cryptochrome 4, a blue-light flavoprotein. In this perspective, we review how computational approaches have shaped our molecular understanding of cryptochrome-based magnetoreception. We organize the discussion around the three steps that connect light absorption to a cellular signal: the photochemical step, in which light absorption by FAD drives a hole-hopping electron-transfer cascade along a conserved tryptophan tetrad; the spin-dependent step, in which the resulting radical pair interconverts between singlet and triplet states under the influence of the magnetic field; and the structural step, in which this transient information is converted into a long-lived signaling state. The early electron-transfer events are now described with growing confidence and appear conserved across avian orthologs, although the relative stability of the final radical-pair states remains debated. The spin-dependent step remains more problematic: once the fluctuations of the hyperfine couplings and a realistic number of nuclear spins are included, the predicted magnetic sensitivity at geomagnetic field intensities becomes very small, and explaining the magnitude of the effect is still a central open problem. The postactivation conformational dynamics, involving intrinsically disordered regions, remains the principal challenge. We suggest that atomistic multiscale modeling, integrated with artificial intelligence-based approaches, has become indispensable for connecting the conserved photochemistry to this downstream process.",
  "abstract_shown": true,
  "affiliations": [
    "Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126 Pisa, Italy",
    "Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mariastella Cascone"
    },
    {
      "affs": [
        1
      ],
      "name": "Lorenzo Cupellini",
      "orcid": "0000-0003-0848-2908"
    },
    {
      "affs": [
        1
      ],
      "name": "Benedetta Mennucci",
      "orcid": "0000-0002-4394-0129"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0rmg17a2fzppg.bib",
  "cited_by": 0,
  "doi": "10.1021/acs.biochem.6c00516",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13738347/",
  "id": "0rmg17a2fzppg",
  "issns": [
    "0006-2960",
    "1520-4995"
  ],
  "landing_url": "https://doi.org/10.1021/acs.biochem.6c00516",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Perspective"
    ],
    [
      "openalex",
      "1304|Electromagnetic Fields and Biological Effects"
    ]
  ],
  "openalex": "W7223085728",
  "pdf_url": "https://pubs.acs.org/bichaw/article-pdf/doi/10.1021/acs.biochem.6c00516/68935694/acs.biochem.6c00516.pdf",
  "pmcid": "PMC13738347",
  "pmid": "42975165",
  "published": "2026-10-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0rmg17a2fzppg.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:23:20Z",
      "native_id": "PMC13738347",
      "source": "pmc",
      "url": "https://doi.org/10.1021/acs.biochem.6c00516"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1304|Electromagnetic Fields and Biological Effects",
      "subfield": "biophysics"
    }
  ],
  "title": "What Computational Simulations Tell Us about Cryptochromes in Magnetoreception",
  "title_text": "What Computational Simulations Tell Us about Cryptochromes in Magnetoreception",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:23:20Z",
  "url": "https://research.draconitic.com/paper/0rmg17a2fzppg",
  "venue": "Biochemistry",
  "versions": []
}