Inverse docking based screening and identification of protein targets for Cassiarin alkaloids against Plasmodium falciparum

Abstract

Various reports have shown Cassiarin alkaloids, selective in vitro activities against various strains of Plasmodium falciparum with low cytotoxicity, which indicates their possible candidature as antimalarial drug. However, poor recognition of their protein targets and molecular binding behaviour, certainly limits their exploration as antimalarial drug candidature. To address this, we utilises inverse screening, based on three different docking methodologies in order to find their most putative protein targets. In our study, we screened 1047 protein structures from protein data bank, which belongs to 147 different proteins. Our investigation identified 16 protein targets for Cassiarins. In few cases of identified protein targets, the binding site was poorly studied, which encouraged us to perform comparative sequence and structural studies with their homologous proteins, like as in case of Kelch motif associated protein, Armadillo repeats only protein and Methionine aminopeptidase 1b. In our study, we also found Tryptophanyl-tRNA synthetase and 1-Deoxy-D-Xylose-5-phosphate reductoisomerase proteins are the most common targets for Cassiarins. Keywords: Plasmodium falciparum, Inverse docking, Cassiarin alkaloids, Proteomics