{
  "abstract": "The molecular determinants governing TRPC6 stabilization and its interaction with caveolin-1 (CAV1) remain poorly defined, despite their critical role in caveolae organization and signaling. The absence of atomistic structural models has hindered a mechanistic understanding of how TRPC6 is recruited to, and stabilized within, caveolar microdomains. Here, we combine all-atom molecular dynamics simulations with MM/PBSA calculations to characterize the TRPC6–CAV1 complex at atomic resolution. To preserve a biologically realistic membrane environment, harmonic restraints were applied to transmembrane and membrane-embedded regions of both proteins, while the cytosolic TRPC6 N-terminus and solvent-exposed edges of the CAV1 scaffolding domain were kept fully flexible, allowing the putative caveolin-binding motif to explore conformational space and form dynamic contacts. This protocol maintained overall structural integrity while capturing physiologically relevant flexibility at the interaction surface. MM/PBSA analysis revealed a highly favorable binding free energy (ΔG_binding = −255.9 ± 1.6 kJ/mol), dominated by electrostatic contributions and reinforced by hydrophobic and aromatic interactions. Per-residue energy decomposition identified an acidic patch in TRPC6 (residues 30–41) that engages a complementary basic, amphipathic segment in CAV1 (residues 85–106), defining a cooperative, reversible binding interface. These findings provide the first atomistic description of TRPC6 recruitment by CAV1 and establish a quantitative framework for the rational design of strategies to selectively modulate this interaction. Highlight Established the first atomistic model of the TRPC6–CAV1 interaction in caveolae Combined all-atom MD simulations with restrained membrane-embedded protein models Interface analysis shows reversible noncovalent binding via transient H-bonds and salt bridges MM/PBSA revealed strong electrostatic-driven binding of the TRPC6–CAV1 complex Identified an acidic TRPC6 N-terminal hotspot engaging a basic amphipathic CAV1 region Graphical Abstract",
  "abstract_shown": true,
  "affiliations": [
    "University of Texas Medical Branch"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "O. K. Polat"
    },
    {
      "name": "S. Bazsefidpar"
    },
    {
      "name": "A. Rodriguez"
    },
    {
      "name": "M. X. Mori"
    },
    {
      "name": "H. Mosadeghi"
    },
    {
      "name": "A. K. Israni"
    },
    {
      "name": "K. M. Koss"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/22rbtymdc5n6c.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.09.750526",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750526v1.full",
  "id": "22rbtymdc5n6c",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750526v1",
  "language": null,
  "licence": "PDM-1.0",
  "licence_label": "Public domain",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/publicdomain/mark/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "1307|Caveolin-1 and cellular processes"
    ]
  ],
  "openalex": "W7212125694",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750526v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/22rbtymdc5n6c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:04Z",
      "native_id": "10.64898/2026.09.09.750526",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750526v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Atomistic Insights into TRPC6/Caveolin-1 Interactions Interface via All- Atom Molecular Dynamics Simulations: Structural and Energetic Basis for Selective Modulation",
  "title_text": "Atomistic Insights into TRPC6/Caveolin-1 Interactions Interface via All- Atom Molecular Dynamics Simulations: Structural and Energetic Basis for Selective Modulation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:04Z",
  "url": "https://research.draconitic.com/paper/22rbtymdc5n6c",
  "venue": "bioRxiv",
  "versions": []
}