{
  "abstract": "The Angiotensin II type-2 receptor (AGTR2) is a G protein-coupled receptor (GPCR) that mediates vasodilatory, anti-proliferative, and cardioprotective responses as part of the renin–angiotensin system (RAS). However, the precise structural dynamics underlying its ligand-specific activation remain incompletely understood. In this study, we performed long-timescale molecular dynamics (MD) simulations to investigate how Angiotensin peptides differentially modulate the structural dynamics of AGTR2 in both inactive- and active-like conformations and to elucidate ligand-specific modulation of AGTR2 in the RAS protective arm. Ang II stabilized a ‘Locked Active State’ through compact TM3–TM6 distances, persistent hydrogen bonding (PHE8–LYS2155.42), salt bridges (ARG2-ASP2796.58, ARG2-ASP2977.32), hydrophobic contacts (TRP1002.60, MET1283.36), and rotameric locking of micro-switches. These interactions stabilized Helix 8, enhancing dynamic network connectivity and supporting ligand-dependent activation-related conformational tendencies rather than a full canonical GPCR activation transition. Conversely, Ang1–7 induced a ‘Flexible Intermediate State’ characterized by weaker interactions (PRO7–THR1253.33), dynamic instability at the Helix 8 interface, and increased conformational sampling. Activation motif analyses (CWxP, PIF, E/DRY, NPxxY), DCC maps, CP, DRIN metrics, and PCA confirmed distinct signaling features for each ligand. This study provides a dual functional profile for AGTR2, where Ang II acts as a strong conformational stabilizer promoting activation-related dynamic features, while Ang 1–7 serves as a dynamic modulator. These findings contribute to a structural and dynamic framework for understanding AGTR2 signaling and supporting its therapeutic potential in fine-tuning cardiovascular responses within the RAS.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biophysics, Faculty of Medicine, Erzincan Binali Yildirim University",
    "Department of Medical Biochemistry, Akdeniz University Medical School",
    "Department of Mathematics and Science Education, Akdeniz University",
    "Department of Biophysics, Akdeniz University Medical School"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ekrem Yasar"
    },
    {
      "affs": [
        1
      ],
      "name": "Segun Dogru"
    },
    {
      "affs": [
        2
      ],
      "name": "Erol Eroglu"
    },
    {
      "affs": [
        3
      ],
      "name": "Nazmi Yaras"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8f8ehmrax1vs9.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-40510-w",
  "fulltext_url": "https://doi.org/10.1038/s41598-026-40510-w",
  "id": "8f8ehmrax1vs9",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://doi.org/10.1038/s41598-026-40510-w",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7169805314",
  "pdf_url": "https://www.nature.com/articles/s41598-026-40510-w_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/8f8ehmrax1vs9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:56Z",
      "native_id": "2c619177e864437597de4b1045b89226",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41598-026-40510-w"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Distinct conformational dynamics of the type-2 Angiotensin II receptor bound to Angiotensin II and Angiotensin (1–7)",
  "title_text": "Distinct conformational dynamics of the type-2 Angiotensin II receptor bound to Angiotensin II and Angiotensin (1–7)",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:56Z",
  "url": "https://research.draconitic.com/paper/8f8ehmrax1vs9",
  "venue": "Scientific Reports",
  "versions": []
}