{
  "abstract": "Metabolites are substrates, products, cofactors, and regulators, but protein-protein interaction networks do not represent their potential to organize proteins across conventional pathway boundaries. Using the LIGMAP virtual-screening algorithm, we mapped 308 human metabolite codes to pockets in monomers, dimer interfaces, and non-interface sites in dimers and represented attractive or repulsive COLIG states involving pairs of metabolites in the same pocket. On a fixed cohort of 3,938 proteins, the mean coverage of 104 strict non-enzyme pathways was 44.6% for LIGMAP, 70.1% for STRING, and 82.5% for STRING+LIGMAP; the union placed 86.3% of eligible proteins in the largest connected component and 95.1% in the two largest components. STRING+LIGMAP protein coverage was 88.0% for 68 enzyme-only pathways and 88.9% for 1,283 mixed pathways. In pathway-held-out, degree-matched prediction, adding LIGMAP to degree plus STRING increased the mean area under the precision-recall curve from 0.651 to 0.660 (paired P = 0.024); adding BioLiP2 increased it to 0.663 (paired P = 0.005). Ancient-only and non-ancient-only subnetworks were each globally connected; ancient features were denser, whereas non-ancient features covered more proteins and pathways. At the full 5,426-protein scale, retaining only features assigned to 2-100 proteins recovered 698 of 1,691 strict non-enzyme reference edges (41.3%) and exceeded both protein-label and exact bipartite degree-preserving nulls. Uncapped recovery approached saturation and lost identity-selective enrichment. Experimentally established metabolite-dependent complexes validate the local mechanism independently of LIGMAP; LIGMAP fully recovered two of seven stringent direct mechanisms and all three broader serial axes examined. Our findings reveal a global metabolite-mediated architecture with the capacity to coordinate proteins across otherwise distinct cellular systems.",
  "abstract_shown": true,
  "affiliations": [
    "Georgia Institute of Technology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "J. Skolnick"
    },
    {
      "name": "B. Srinivasan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/69gx1cj9qb1wy.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.28.747909",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747909v1.full",
  "id": "69gx1cj9qb1wy",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747909v1",
  "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|Bioinformatics and Genomic Networks"
    ]
  ],
  "openalex": "W7208720258",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747909v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/69gx1cj9qb1wy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:14Z",
      "native_id": "10.64898/2026.08.28.747909",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747909v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "The human metabolite - protein interactome reveals a global layer of cellular coordination",
  "title_text": "The human metabolite - protein interactome reveals a global layer of cellular coordination",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:14Z",
  "url": "https://research.draconitic.com/paper/69gx1cj9qb1wy",
  "venue": "bioRxiv",
  "versions": []
}