{
  "abstract": "Predicting protein-ligand complex structures is a central challenge in drug discovery. While recent co-folding models such as AlphaFold-3 achieve accurate structure prediction, they fail to generalize to underexplored binding interfaces - systematically misplacing ligands, particularly for allosteric or structurally novel targets. To address this gap, we present ACER (A daptive Co-folding via pocket E xploration and pose R anking), a training-free framework that (a) enables co-folding models to systematically explore alternative binding pockets, and (b) leverages the discovered pockets to increase pose accuracy. Our method enables the efficient discovery of non-prevalent pockets without prior expert knowledge. ACER improves pocket discovery and pose accuracy on allosteric targets and structurally novel complexes, successfully modeling binding interfaces that are under-represented or absent from the training set. Our results demonstrate how improved sampling dynamics enhance the generalisability of co-folding models without retraining.",
  "abstract_shown": true,
  "affiliations": [
    "Eindhoven University of Technology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "N. Vithayapalert"
    },
    {
      "affs": [
        0
      ],
      "name": "F. Grisoni"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/68xe52kaxjnyp.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.06.02.728568",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.06.02.728568v2.full",
  "id": "68xe52kaxjnyp",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.06.02.728568v2",
  "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": "W7163670881",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.06.02.728568v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/68xe52kaxjnyp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:40Z",
      "native_id": "10.64898/2026.06.02.728568",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.06.02.728568v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Towards Generalizable Protein-ligand Co-folding with ACER",
  "title_text": "Towards Generalizable Protein-ligand Co-folding with ACER",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:40Z",
  "url": "https://research.draconitic.com/paper/68xe52kaxjnyp",
  "venue": "bioRxiv",
  "versions": []
}