Research article

Quantum chemical calculations on calcium oxalate and dolichin A and their binding efficacy to lactoferrin: An in silico study using DFT, molecular docking, and molecular dynamics simulations

  • Received: 29 January 2024 Revised: 19 March 2024 Accepted: 25 March 2024 Published: 07 April 2024
  • Lactoferrin, a member of the transferrin family, is one of the promoter proteins for calcium oxalate-type kidney stone formation. It exhibits a remarkable ability to interact with metals and oxalate ions. The prevalence of calcium oxalate in kidney stones was confirmed by the Fourier transform infrared spectra. The quantum chemical properties of calcium oxalate and dolichin A calculated by density functional theory and time-dependent density functional theory indicate their potential for hydrogen bonding and nonbonding interactions with the receptor proteins. From molecular docking analysis, the binding free energy of dolichin A was −7.78 kcal/mol, which was the best of twenty-four phytochemicals from Macrotyloma uniflorum, and that of calcium oxalate was −3.86 kcal/mol to lactoferrin. Furthermore, dolichin A having favorable physicochemical and pharmacokinetic properties offers post molecular dynamics molecular mechanics generalized Born surface area free energy of −17.61 ± 4.03 kcal/mol, indicating the strong binding interactions, and, therefore, it acts as a potential inhibitor of the lactoferrin.

    Citation: Arjun Acharya, Madan Khanal, Rajesh Maharjan, Kalpana Gyawali, Bhoj Raj Luitel, Rameshwar Adhikari, Deependra Das Mulmi, Tika Ram Lamichhane, Hari Prasad Lamichhane. Quantum chemical calculations on calcium oxalate and dolichin A and their binding efficacy to lactoferrin: An in silico study using DFT, molecular docking, and molecular dynamics simulations[J]. AIMS Biophysics, 2024, 11(2): 142-165. doi: 10.3934/biophy.2024010

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  • Lactoferrin, a member of the transferrin family, is one of the promoter proteins for calcium oxalate-type kidney stone formation. It exhibits a remarkable ability to interact with metals and oxalate ions. The prevalence of calcium oxalate in kidney stones was confirmed by the Fourier transform infrared spectra. The quantum chemical properties of calcium oxalate and dolichin A calculated by density functional theory and time-dependent density functional theory indicate their potential for hydrogen bonding and nonbonding interactions with the receptor proteins. From molecular docking analysis, the binding free energy of dolichin A was −7.78 kcal/mol, which was the best of twenty-four phytochemicals from Macrotyloma uniflorum, and that of calcium oxalate was −3.86 kcal/mol to lactoferrin. Furthermore, dolichin A having favorable physicochemical and pharmacokinetic properties offers post molecular dynamics molecular mechanics generalized Born surface area free energy of −17.61 ± 4.03 kcal/mol, indicating the strong binding interactions, and, therefore, it acts as a potential inhibitor of the lactoferrin.



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    Acknowledgments



    We would like to express our gratitude to Prof. Dr. Rajendra Parajuli and Asst. Prof. Pitamber Shrestha for their invaluable support in providing access to Gaussian 16W. Additionally, we extend our sincere thanks to Dr. Rabindra Tamang, Dr. Purushottam Parajuli, Dr. Anjit Phuyal, and Dr. Milan Gyawali for their unwavering assistance in the collection of samples. Lastly, we are deeply grateful to Mr. Bidit Lamsal and Mr. Yub Narayan Thapa for their support in generating the FTIR spectra. This research is partially supported by the Research Endowment Fund (REF) at Tribhuvan University, Rector's Office, Research Directorate, Kathmandu, Nepal.

    Conflict of interest



    The authors declare that there are no conflicts of interest.

    Ethics approval and consent to participate



    This study was conducted with the approval of the Institutional Review Committee of the Institute of Medicine, Tribhuvan University Teaching Hospital, Maharajgunj, Kathmandu, Nepal with an approval number of 117 (6-11) E2 079/080. Informed consent was received from participants or their parents or legal guardians.

    Data availability



    The data supporting the findings of this study are available within the article and its supplementary materials.

    Authors' contributions



    A Acharya: Conceived and designed the experiments, analyzed data, and drafted the manuscript
    M Khanal: Data analysis, manuscript writing, and revised the manuscript
    R Maharjan: Technical support, critical feedback, and revised the manuscript
    K Gyawali: Critical feedback and revised the manuscript
    BR Luitel: Critical feedback, data analysis, and revised the manuscript
    R Adhikari: Critical feedback, data analysis, and revised the manuscript
    DD Mulmi: Critical feedback and revised the manuscript
    TR Lamichhane: Technical support, critical feedback, data analysis, and revised the manuscript
    HP Lamichhane: Critical feedback, data analysis, and revised the manuscript

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