Identification of promising inhibitors for Plasmodium haemoglobinase Falcipain-2, using virtual screening, molecular docking, and MD Simulation

Abstract

BackgroundFalcipain-2 (FP-2), the major haemoglobinase of the human malaria parasite Plasmodium falciparum is currently gaining clinical significance as a drug target of choice in combating malaria. But due to resistance of the malaria parasite against well-known available drugs, the chemotherapy of malaria has become more complex and challenging. Prior attempts to develop peptide-based drugs against them have been futile due to their susceptibility to degradation by host enzymes. MethodsWithin this context, computational methods namely High Through- put Screening using PyRx Virtual Screening software, Molecular Docking by docking software Autodock followed by Molecular Dynamics Simulations and PCA by GROMACS simulation software were used to select, from a pool of candidate molecules in a molecular database, a subset of compounds for experimental validation. One of the major goals is to increase the probabilities of identifying active compounds. ResultsWe have reported a computer-aided design of four new nonpeptidic inhibitors against FP-2. During the design, an initial virtual library of PubChem database was focused down to 800 drug-like compounds and finally, virtual screened and docked to identify four promising compounds which were further equilibriated by Molecular Dynamics Simulations. ConclusionThese can be further analyzed in-depth to develop antimalarial drugs to treat resistant strains of Plasmodium.