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Molecular Dynamics Simulation Study on the Effect of Oxali-Palladium as a Catalytic Inhibitor of Human Topoisomerase IIα

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Abstract

Among the many anticancer agents targeting topoisomerase IIα enzyme, palladium (II) analogues have gained in popularity as a promising enzyme inhibitor. In this article, molecular docking method and molecular dynamics (MD) simulations were employed to study the mechanism through which oxali-palladium (oxali-Pd) inhibits the enzymatic activity of human topo IIα. The results of docking simulation confirm the inhibitory effects of oxali-Pd on the catalytic core of topoisomerase IIα enzyme through a non-competitive process. Also, it is suggested that oxali-Pd might intercalate within the DNA bases according to the topo IIα dynamicity as well. The results of MD simulations reveal that oxali-Pd is surrounded by Arg713, Ser714, Lys723, GLN726, Ser 763, Met766, Thr767, Asn770, Leu771, Glu854, Gly855, and Arg929 residues of protein. The average value of ΔGsolv is about − 93.1 kJ.mol−1 for protein and − 95.1 kJ.mol−1 for complex. The average values of Coulombic and Lennard–Jones interaction energies are calculated to be about − 78.1 ± 18.9 and − 81.8 ± 10.2 kJ.mol−1, respectively. These interaction energy values demonstrate the both electrostatic and van der Waals forces are important in complex formation between topo IIα protein and oxali-Pd molecule. Therefore, based on the data obtained from this study, oxali-Pd acts as a catalytic inhibitor of human topo IIα and is not a poison to the enzyme.

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Acknowledgement

The authors are grateful to Kharazmi University of Tehran and the Iran National Science Foundation (No: 99004364) for their financial support.

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Authors and Affiliations

  1. Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

    Nadia Tavakoli & Adeleh Divsalar

  2. State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China

    Behafarid Ghalandari & Xianting Ding

  3. Department of Physical Chemistry, Faculty of Sciences, Tarbiat Modares University, Tehran, Iran

    Farideh Badalkhani-Khamseh

Authors
  1. Nadia Tavakoli
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  2. Behafarid Ghalandari
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  3. Farideh Badalkhani-Khamseh
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  4. Xianting Ding
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  5. Adeleh Divsalar
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Correspondence to Adeleh Divsalar.

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Tavakoli, N., Ghalandari, B., Badalkhani-Khamseh, F. et al. Molecular Dynamics Simulation Study on the Effect of Oxali-Palladium as a Catalytic Inhibitor of Human Topoisomerase IIα. Iran J Sci Technol Trans Sci 46, 1575–1582 (2022). https://doi.org/10.1007/s40995-022-01384-5

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  • DOI: https://doi.org/10.1007/s40995-022-01384-5

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