{
  "abstract": "Structure-aware proteolysis prediction often ranks candidate cleavage sites using solvent accessibility from static protein structures, yet this assumption is rarely tested against native-state cleavage data. We examined this problem using AprX, a serralysin-family protease that readily hydrolyses caseins but shows lower activity toward native whey proteins. Across six bovine milk proteins, sequence compatibility and local scissile-bond accessibility did not separate caseins from whey proteins. In contrast, accessibility fell progressively in whey proteins as the required contiguous substrate window increased, reaching 0% across the working P4-P4' footprint, while all evaluable casein windows remained accessible in isolated-chain ensembles. Local remodelling showed that whey segments could still adopt AprX-compatible backbone geometry. An external thermolysin benchmark rejected a rigid whole-protein clash metric, but did not alter the contiguous-accessibility result. These findings identify footprint-scale accessibility as a distinct structural variable and show why single-residue solvent exposure can overestimate protease accessibility in folded proteins.",
  "abstract_shown": true,
  "affiliations": [
    "University College Cork"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "A. Sinha"
    },
    {
      "name": "T. Racca"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fy0x1spxgtkz9.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.02.756230",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756230v1.full",
  "id": "fy0x1spxgtkz9",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756230v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7220864391",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756230v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fy0x1spxgtkz9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:20Z",
      "native_id": "10.64898/2026.10.02.756230",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756230v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Substrate accessibility of bovine milk proteins to a Pseudomonas metalloprotease reveals why caseins are more readily hydrolysed than whey proteins",
  "title_text": "Substrate accessibility of bovine milk proteins to a Pseudomonas metalloprotease reveals why caseins are more readily hydrolysed than whey proteins",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:20Z",
  "url": "https://research.draconitic.com/paper/fy0x1spxgtkz9",
  "venue": "bioRxiv",
  "versions": []
}