A Comprehensive In Silico Study Towards Understanding the Inhibitory Mechanism of Lactoperoxidase by Dapsone and Propofol

Author(s): Rameez Jabeer Khan, Rajat Kumar Jha, Gizachew Muluneh Amera, Jayaraman Muthukumaran, Rashmi Prabha Singh*, Amit Kumar Singh*

Journal Name: Current Computer-Aided Drug Design

Volume 17 , Issue 4 , 2021

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Graphical Abstract:


Introduction: Lactoperoxidase (LPO) is a member of the mammalian heme peroxidase family and is an enzyme of the innate immune system. It possesses a covalently linked heme prosthetic group (a derivative of protoporphyrin IX) in its active site. LPO catalyzes the oxidation of halides and pseudohalides in the presence of hydrogen peroxide (H2O2) and shows a broad range of the antimicrobial activity.

Methods: In this study, we have used two pharmaceutically important drug molecules, namely dapsone and propofol, which were earlier reported as potent inhibitors of LPO. At the same time, the stereochemistry and mode of binding of dapsone and propofol to LPO are still not known because of the lack of the crystal structures of LPO with these two drugs. In order to fill this gap, we utilized molecular docking and molecular dynamics (MD) simulation studies of LPO in its native and complex forms with dapsone and propofol.

Results: From the docking results, the estimated binding free energies (ΔG) of -9.25 kcal/mol (Ki = 0.16 μM) and -7.05 kcal/mol (Ki = 6.79 μM) were observed for dapsone, and propofol, respectively. The standard error of the Auto Dock program is 2.5 kcal/mol; therefore, molecular docking results alone were inconclusive.

Conclusion: To further validate the docking results, we performed MD simulation on unbound, and two drugs bounded LPO structures. Interestingly, MD simulations results explained that the structural stability of LPO-Propofol complex was higher than LPO-Dapsone complex. The results obtained from this study establish the mode of binding and interaction pattern of the dapsone and propofol to LPO as inhibitors.

Keywords: Lactoperoxidase, propofol, dapsone, in silico, molecular docking, heme peroxidase superfamily.

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Article Details

Year: 2021
Published on: 27 June, 2020
Page: [550 - 559]
Pages: 10
DOI: 10.2174/1573409916666200628104134
Price: $65

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