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In silico elucidation of the interactions of thymoquinone analogues with phosphatase and tensin homolog (PTEN)

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Abstract

Thymoquinone, as one of the main constituents of black seed, has impressive medicinal properties. In the present study, the interaction of this compound and its five derivatives with phosphatase and tensin homolog (PTEN), which is the second most highly mutated protein in a wide variety of human cancers, has been studied using molecular docking and molecular dynamics simulation studies. Molecular docking results show that thymoquinone derivatives bounded to PTEN and have relatively suitable binding energies. Analysis of molecular dynamics (MD) simulation results suggested that the interactions between thymoquinone analogues and PTEN are stable, and the binding of the ligands limited the flexibility of key residues in the binding site of this protein. Furthermore, data analysis of all the compounds indicates the predominant roles of hydrogen bonds and van der Waals interactions in the ligand binding process to PTEN. Finally, adsorption, distribution, metabolism, and excretion (ADME) analysis predicted that all of these compounds obeyed Lipinski’s RO5 and did not show any violation; therefore, all of these compounds can act like a drug. Results of the current study could shed some light on the binding of thymoquinone analogues to PTEN for further experimental studies.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Payame Noor University (PNU), Tehran, Iran

    Leila Hokmabady

  2. Iliya Computational Research Center (ICRC), Isfahan, Iran

    Najmeh Fani

  3. Department of Chemistry, Isfahan University of Technology, Isfahan, Iran

    Najmeh Fani

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  1. Leila Hokmabady
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The authors contributed to the study conception and design. The first draft of the manuscript was written by Hokmabady, and authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Hokmabady, L., Fani, N. In silico elucidation of the interactions of thymoquinone analogues with phosphatase and tensin homolog (PTEN). J Mol Model 28, 321 (2022). https://doi.org/10.1007/s00894-022-05318-1

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