{
  "abstract": "Cytoplasmic dynein is a complex hexameric AAA+ motor protein essential for intracellular transport, yet the structural mechanisms and domain cooperativity driving its mechanochemical cycle remain incompletely understood. In this study, we utilize a dual-basin structure-based model (SBM) to simulate the full-length dynein cycle in the presence of microtubules. Rather than a single concerted transition, our results reveal that dynein moves through discrete, on-pathway conformational intermediates, including a transient, ADP-bound state that bridges the pre- and post-powerstroke configurations. We identify four key regulatory interfaces (AAA1-subdomains, AAA1–AAA2, AAA3–AAA4, and AAA5–AAA6) that function as checkpoints to couple the AAA+ ring changes to power- and recovery stroke. Crucially, we elucidate the regulatory roles of the non-dominant domains: suppressing AAA3 disrupts recovery-stroke progression and linker relocation, while suppressing AAA4 selectively impairs linker stabilization and docking. Together, these findings demonstrate that dynein's force generation relies on a highly coordinated allosteric network across the entire AAA+ ring.",
  "abstract_shown": true,
  "affiliations": [
    "School of Chemical Sciences",
    "Indian Association for the Cultivation of Science"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Pradipta Kumar Das"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Biman Jana",
      "orcid": "0000-0001-7684-1963"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/12p3hgtezexc5.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010025/v1",
  "fulltext_url": null,
  "id": "12p3hgtezexc5",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010025/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",
      "1307|Microtubule and mitosis dynamics"
    ]
  ],
  "openalex": "W7220845821",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010025/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/12p3hgtezexc5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010025",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010025/v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Microtubule and mitosis dynamics",
      "subfield": "cell-biology"
    }
  ],
  "title": "Exploring intermediates in mechanochemical cycle and mechanism of regulation of full-length Dynein",
  "title_text": "Exploring intermediates in mechanochemical cycle and mechanism of regulation of full-length Dynein",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/12p3hgtezexc5",
  "venue": "ChemRxiv",
  "versions": []
}