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.