Molecular docking and dynamics studies on plasmepsin V of malarial parasite Plasmodium vivax

Malaria is a fatal disease caused by plasmodium parasites and is transmitted through female anopheles mosquitoes. These parasites dwell on human erythrocytes for most of their life sequence. The proteins involved in Plasmodium Export Element (PEXEL) cleavage are essential for the parasite's survival and for transmission of virulence. Plasmepsin V (PMV), an aspartic protease, plays a major role in the cleavage of the PEXEL motifs and their export to the host. In this study, we have screened drug-like molecules to inhibit PMV, thereby acting as a potential drug against malaria. Interestingly, molecular docking studies suggest that the molecules Zinc14544904 and Lopinavir showed good binding affinity toward PMV of P. vivax (pvPMV). In addition, molecular dynamics results suggest that the screened molecules were found to be stable and occupy the binding pockets throughout the 10 ns run. The presence of intermolecular hydrogen bonding between ligand and pvPMV was observed throughout the simulation duration. The active site residues such as Thr317, Ser316, Gly315, Leu179, Cys140, and Glu141 were hypothesized as functionally important residues and were involved in hydrogen bonding and hydrophobic interaction with ligand molecules. Thus, from molecular docking and dynamics simulation results, we suggest that compounds Zinc14544904 and Lopinavir could inhibit pvPMV, and can be used as potential drugs for the treatment of multidrug resistant Malaria.