{
  "abstract": "Over the centuries, hyperlipidaemia has been recognised as a major risk factor contributing to cardiovascular disease (CVD). Current research increasingly explores natural compounds such as flavonoids for their potential lipid-lowering effects. This study evaluated pharmacological potential of flavonoids to identify strong inhibitors for target receptor, Proprotein Convertase Subtilisin/Kexin Type (PCSK9). A total of 29 compounds, including one FDA-approved drugs were screened for drug-likeness and ADMET properties, followed by molecular docking and Molecular Dynamics (MD) simulations using PCSK9 receptor containing glucose and sodium (PDB ID: 5OCA). This complex was chosen due to their functional relevance to cholesterol metabolism. As a results, 24 compounds satisfied Lipinski’s Rule of Five and exhibited favourable drug-likeness and toxicity profiles. Simvastatin (control) was discovered to bind into the pocket B binding site along with seven flavonoids; Diosmetin, Eupatorin, Isorhamnetin, Myricetin, Petunidin, Sinensetin, and Tilianin. These flavonoids displayed docking energies ranging from −8.0 to −10.2 kcal/mol. Tilianin showed the strongest affinity (−10.2 kcal/mol), while Simvastatin bound with −9.1 kcal/mol. MD simulations confirmed that the PCSK9-ligand complexes remained structurally stable throughout a 100 ns trajectory. MM/PBSA analysis further supported the binding interactions, revealing free energies values ranging from −17 to −30.41 kcal/mol. Among the flavonoids evaluated, Tilianin, Myricetin, and Sinensetin demonstrate the most favourable interaction profiles. These finding suggest that the selected flavonoids have strong potential as promising anti-hyperlipidaemic candidates targeting PCSK9.",
  "abstract_shown": true,
  "affiliations": [
    "School of Graduate Studies, Postgraduate Centre Management and Science University, University Drive, Shah Alam, Selangor, Malaysia",
    "Faculty of Health and Life Sciences, Management and Science University, University Drive, Shah Alam, Selangor, Malaysia",
    "Institute for Medical Research, National Institutes of Health Malaysia, Shah Alam, Selangor, Malaysia"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nurnazira Hanis Mustaffar Kamal"
    },
    {
      "affs": [
        1
      ],
      "name": "Nurul Azira Ismail"
    },
    {
      "affs": [
        2
      ],
      "name": "Ernie Zuraida Ali"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aqpr3wz0ykwx7.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0346073",
  "fulltext_url": null,
  "id": "aqpr3wz0ykwx7",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0346073",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1703|Computational Drug Discovery Methods"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Biochemical simulations"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Lipids/Cholesterol"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Biochemical simulations"
    ],
    [
      "plos",
      "/Biology and life sciences/Toxicology/Toxicity"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology/Toxicity"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmacology/Drug interactions"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Computational chemistry/Molecular docking"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Computational chemistry/Molecular dynamics"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Physical chemistry/Chemical bonding/Hydrogen bonding"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Thermodynamics/Free energy"
    ]
  ],
  "openalex": "W7221194623",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0346073&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/aqpr3wz0ykwx7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:30Z",
      "native_id": "10.1371/journal.pone.0346073",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0346073"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "plos:computational chemistry",
      "subfield": "theoretical"
    },
    {
      "field": "medicine",
      "origin": "plos:toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Identification of flavonoids from natural products against hyperlipidaemia through computational approaches",
  "title_text": "Identification of flavonoids from natural products against hyperlipidaemia through computational approaches",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:30Z",
  "url": "https://research.draconitic.com/paper/aqpr3wz0ykwx7",
  "venue": "PLOS One",
  "versions": []
}