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<p>Ovarian cancer remains one of the most lethal gynecological malignancies due to late diagnosis, limited treatment options, and high recurrence rates. Recent evidence highlights the ubiquitin–proteasome system as a key contributor to cancer progression, with ubiquitin-conjugating enzyme E2 J1 (UBE2J1) emerging as a potential oncogenic target. In this study, a comprehensive in silico drug discovery approach was applied to identify natural phytochemicals capable of inhibiting UBE2J1. Sequence and structural modeling confirmed the reliability of the predicted protein conformation, while protein-protein interaction analysis underscored its central role in ubiquitination pathways. Five plant-derived compounds were screened through molecular docking, among which Withaferin A exhibited the strongest binding affinity (– 8.4&#xa0;kcal/mol), forming stable hydrogen bonds and hydrophobic interactions with key active site residues. Molecular dynamics simulations further demonstrated the stability of the protein–ligand complex, with favorable RMSD, RMSF, and radius of gyration profiles. ADMET and drug-likeness evaluations revealed that Withaferin A complies with Lipinski’s rule of five, possesses good intestinal absorption, and shows non-carcinogenic and non-mutagenic properties. Binding free energy calculations using MM/GBSA supported its strong affinity toward UBE2J1. These findings highlight Withaferin A as a promising natural inhibitor of UBE2J1 and provide a foundation for future experimental validation aimed at developing targeted therapies against ovarian cancer.</p>

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Computational identification of natural phytochemicals as potential inhibitors of UBE2J1 causing ovarian cancer

  • 期刊论文

  • 发表日期：

    2026年7月31日

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  • Zujaja Rehman,
  • Ejaz Rasul,
  • Wisha Asif,
  • Rabail Afzal,
  • Nouman Ali,
  • Nimra Hanif,
  • Muhammad Salik Kamran

摘要

Ovarian cancer remains one of the most lethal gynecological malignancies due to late diagnosis, limited treatment options, and high recurrence rates. Recent evidence highlights the ubiquitin–proteasome system as a key contributor to cancer progression, with ubiquitin-conjugating enzyme E2 J1 (UBE2J1) emerging as a potential oncogenic target. In this study, a comprehensive in silico drug discovery approach was applied to identify natural phytochemicals capable of inhibiting UBE2J1. Sequence and structural modeling confirmed the reliability of the predicted protein conformation, while protein-protein interaction analysis underscored its central role in ubiquitination pathways. Five plant-derived compounds were screened through molecular docking, among which Withaferin A exhibited the strongest binding affinity (– 8.4 kcal/mol), forming stable hydrogen bonds and hydrophobic interactions with key active site residues. Molecular dynamics simulations further demonstrated the stability of the protein–ligand complex, with favorable RMSD, RMSF, and radius of gyration profiles. ADMET and drug-likeness evaluations revealed that Withaferin A complies with Lipinski’s rule of five, possesses good intestinal absorption, and shows non-carcinogenic and non-mutagenic properties. Binding free energy calculations using MM/GBSA supported its strong affinity toward UBE2J1. These findings highlight Withaferin A as a promising natural inhibitor of UBE2J1 and provide a foundation for future experimental validation aimed at developing targeted therapies against ovarian cancer.