{
  "abstract": "Large-scale protein structure prediction enables proteome-wide protein-protein interaction (PPI) screening, but distinguishing biologically meaningful interactions from spurious interfaces remains challenging. Here, we develop a scalable framework combining fast, MSA-free ESMFold2 prediction with PAE-guided domain parsing and evidence-based reranking. Three-recycle ESMFold2-Fast achieved 57% acceptable-or-better DockQ scores on FoldBench, comparable to AlphaFold2-Multimer while substantially reducing computation. PAE-guided parsing preserved 98.1% of XL-MS cross-links within parsed domain pairs. We then developed the Structure Prediction and Omics informed Classifier (SPOC)-ESMFold2, which integrates structural features with independent biological evidence to prioritize predicted interactions. SPOC-ESMFold2 achieved an AUROC of 0.93 and AUPR of 0.90, compared with 0.87 and 0.79 for a structural-only classifier. Under a 1:128 positive-to-negative ratio, SPOC-ESMFold2 achieved 17.2% recall at 5% false-discovery rate, substantially outperforming structural confidence metrics alone. This framework enables scalable PPI screening by integrating structural plausibility with orthogonal biological evidence to prioritize candidates for experimental investigation.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Membrane Biology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "J. Xie"
    },
    {
      "name": "M. Li"
    },
    {
      "name": "Y. Chai"
    },
    {
      "name": "G. Ou"
    },
    {
      "name": "W. Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Z. Guo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4evyy5fmhqbe5.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.16.751194",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751194v1.full",
  "id": "4evyy5fmhqbe5",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751194v1",
  "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",
      "bioinformatics"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7213556517",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751194v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4evyy5fmhqbe5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:58Z",
      "native_id": "10.64898/2026.09.16.751194",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751194v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Integrating structural and biological evidence to rerank ESMFold2 protein-protein interactions",
  "title_text": "Integrating structural and biological evidence to rerank ESMFold2 protein-protein interactions",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:58Z",
  "url": "https://research.draconitic.com/paper/4evyy5fmhqbe5",
  "venue": "bioRxiv",
  "versions": []
}