Characterization of Human-malarial Parasite Species based on DHFR and GST Targets Resulting in Changes in Anti-malarial Drug Binding Conformations.

Abstract

In this study, we focused primarily on three anti-malarial drugs, namely chloroquine, mefloquine, and proguanil, and these were tested against two malarial targets DHFR and GST. The species Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax were used for the study. The purpose of this study was to determine the sequence and structural similarity of the proteins DHFR and GST among four Plasmodium species as well as to discover the in silico interactions with the aforementioned drug candidates. Bioinformatics databases, such as PDB, UniProt, DrugBank, PubChem, and tools, and software like Phyre 2.0, Clustal O (1.2.4), AutoDock 4, AutoDock Vina, and Discovery Studio Visualizer were used to determine the evolutionary significance of the Plasmodium species. The variations showed a difference in the binding patterns of drugs with our target proteins. Our finding reveals the Plasmodium spp divergence or convergence as well as the structural and sequential similarity or dissimilarity features. Our result suggests that due to the deviation in the sequences and structures, variations in protein-drug binding patterns have emerged.