STUDIES OF PUTATIVE INSULINASE OF PLASMODIUM FALCIPARUM (3D7) AS DRUG TARGET FOR ARTEMISININ
- Bagyalakshmi1, Puniethaa Prabhu2 , Joram Yam1*
Department of Biotechnology Technology, K. S. Rangasamy College of Technology, Tiruchengode – 637 215, Tamil Nadu, India
Abstract
Malaria is one of the most common infectious diseases in tropical and subtropical regions and more than 240 million causes malaria and 627,000 deaths were reported globally in 2022. Among all the malarial parasites, plasmodium falciparum is the most virulent and associated with more complications. Now these dangerous parasites have developed resistance against most of its drugs. This review focused on the putative insulinase of PF3D7_1118300 genome from plasmodium falciparum as a new target site for artemisinins. Putative insulinase 3D structure was downloaded from UniProt. GROMACS 2022.2 package was used to perform MD simulation in water and all atom OPLS forcefield was used. Artesiminins was downloaded from PubChem. Active site of protein-ligand was predicted by PyMol and their interaction was performed using AutoDock to determine the binding affinities and interaction between phytochemicals and the putative insulinase of PF3D7_1118300 and BIOVIA discovery studio was used to visualized the binding site. Finally, protein-ligand MD simulation was carried out using the GROMACS 2022.2 package. GROMOS96 forcefield was used for protein to generate the topology and PRODRG 2.5 package was used to generate the ligand topology. Simple point charge water model [SPC216] was used to solvate the protein under cubic box. The system was then minimized energy and equilibrated for 100ps under NVT and NPT using 50,000 steps and then simulation production was done. At the end, results were analyzed by root-mean-square deviation, root-mean-square fluctuation and the radius of gyration and solvent-accessible area.
Keywords: plasmodium falciparum, molecular docking, AutoDock, PyMol, GROMACS
