{
  "abstract": "Genetic variation in cervid PRNP influences chronic wasting disease (CWD) susceptibility and progression, but it remains unclear whether disease-associated substitutions produce localized differences in sequence-derived properties relevant to prion protein (PrPC) condensation. We compared a white-tailed deer (WTD) reference sequence with 10 modeled variants on the same mature PrP scaffold (residues 24-233). For each sequence, we calculated intrinsic disorder, FuzDrop per-residue droplet-promoting propensity (pDP) and binding-mode entropy (Sbind), predicted residue-level pKa values, and a discrete-charge summary at pH 7.0. The overall profiles preserve a long N-terminal droplet-promoting region, whereas variant-associated differences are concentrated in selected intervals. In the FuzDrop outputs, residues 126-140 show allele-dependent changes in pDP near the droplet-promoting threshold, and residues 220-230 show variant-specific changes in Sbind, including lower Sbind for S225F/Y and higher Sbind for elk-like Q226E. These differences occur without large changes in overall intrinsic disorder. KaML pKa predictions identify near-neutral titratable sites that provide electrostatic context for these local predictor differences. Independent atomistic simulations of monomeric PrP further detected variant-sensitive backbone behavior and intramolecular contacts involving these intervals. Together, the analysis identifies residues 126-140 and 220-230 as computationally defined candidate intervals that overlap regions implicated independently in prion conversion or CWD fibril structure, motivating direct tests of cervid PrP condensation and maturation.",
  "abstract_shown": true,
  "affiliations": [
    "University of Maryland School of Pharmacy"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "G. W. Dayhoff"
    },
    {
      "name": "L. Dorosh"
    },
    {
      "name": "H. Wille"
    },
    {
      "name": "V. N. Uversky"
    },
    {
      "name": "M. Stepanova"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aeww8mmvhws77.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.27.762346",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762346v1.full",
  "id": "aeww8mmvhws77",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762346v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "1312|Prion Diseases and Protein Misfolding"
    ]
  ],
  "openalex": "W7225110570",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762346v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/aeww8mmvhws77.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:20:51Z",
      "native_id": "10.64898/2026.10.27.762346",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762346v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Predicted condensation-related signatures localize to two C-terminal regions of the prion protein across cervid PRNP variants associated with chronic wasting disease",
  "title_text": "Predicted condensation-related signatures localize to two C-terminal regions of the prion protein across cervid PRNP variants associated with chronic wasting disease",
  "type": "preprint",
  "updated_at": "2026-11-04T00:21:14Z",
  "url": "https://research.draconitic.com/paper/aeww8mmvhws77",
  "venue": "bioRxiv",
  "versions": []
}