An in silico strategy for identification of novel drug targets against Plasmodium falciparum

摘要

The apicomplexan parasite Plasmodium falciparum is responsible for global malaria burden. With the reported resistance to artemisinin chemotherapy, there is an urgent need to maintain early phase drug discovery and identify novel drug targets for successful eradication of the pathogen from the host. In our previous work on comparative genomics study for identification of putative essential genes and therapeutic candidates in P. falciparum, we predicted 11 proteins as anti-malarial drug targets from PlasmoDB database. In this paper, we made an attempt for identification of novel drug targets in P. falciparum genome using a sequence of computational methods from Malaria Parasite Metabolic Pathway database. The study reported the identification of 71 proteins as potential drug targets for anti-malarial interventions. Furthermore, homology modeling and molecular dynamic simulation study of one of the potential drug targets, aminodeoxychorismate lyase, was carried to predict the 3D structure of the protein. Structure and ligand-based drug designing reported MMV019742 from Pathogen Box and TCAMS-141515 from GSK-TCAMS library as potential hits. The reliability of the binding mode of the inhibitors is confirmed by GROMACS for a simulation time of 20 ns in water environment. This will be helpful for experimental validation of the small-molecule inhibitor.