{
  "abstract": "Efficiently exploring the rare conformational states of biomolecules remains a central challenge in molecular dynamics simulation. Here we show, using adenylate kinase as a methodological testbed, that the static structural scores conventionally used to prioritize diffusion-modelgenerated candidates have essentially no power to predict which candidates actually reach a kinetically rare state upon subsequent simulation (AUC = 0.500). Motivated by this finding, we introduce two adaptive strategies — direct PCA-distance targeting and replication of confirmed-hit structures — that achieve significantly higher rare-state hit rates and dwell times than extended conventional molecular dynamics or random-initialization sampling under matched computational budgets, while also enabling, for the first time, statistically stable estimation of rare-macrostate populations. These results show that structural novelty and kinetically meaningful entry into a rare state are not the same property, providing concrete design guidance for generative-model-driven adaptive sampling in other biomolecular systems.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Management of Information Technologies, Kagoshima University, 1-21-35 Korimoto, Kagoshima, Japan, 890-0065"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yoshitake Sakae",
      "orcid": "0000-0001-7204-2021"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8g80dgy3wyt73.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008478/v1",
  "fulltext_url": null,
  "id": "8g80dgy3wyt73",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008478/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7211972563",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008478/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/8g80dgy3wyt73.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15008478",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008478/v3"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Diffusion-Model-Guided Adaptive Sampling of Rare Conformational States in Adenylate Kinase",
  "title_text": "Diffusion-Model-Guided Adaptive Sampling of Rare Conformational States in Adenylate Kinase",
  "type": "preprint",
  "updated_at": "2026-11-06T00:20:51Z",
  "url": "https://research.draconitic.com/paper/8g80dgy3wyt73",
  "venue": "ChemRxiv",
  "versions": []
}