In silico comparative genomics analysis of Plasmodium falciparum for the identification of putative essential genes and therapeutic candidates

• Essential genes and drug target prediction in P. falciparum genome
• 21 proteins are predicted as essential and 11 are prioritized as drug targets.
• Homology modeling and virtual screening study of two uncharacterized proteins
• Molecular docking study of top five compounds through AutoDock 4 software

A sequence of computational methods was used for predicting novel drug targets against drug resistant malaria parasite Plasmodium falciparum. Comparative genomics, orthologous protein analysis among same and other malaria parasites and protein–protein interaction study provide us new insights into determining the essential genes and novel therapeutic candidates. Among the predicted list of 21 essential proteins from unique pathways, 11 proteins were prioritized as anti-malarial drug targets. As a case study, we built homology models of two uncharacterized proteins using MODELLER v9.13 software from possible templates. Functional annotation of these proteins was done by the InterPro databases and from ProBiS server by comparison of predicted binding site residues. The model has been subjected to in silico docking study with screened potent lead compounds from the ZINC database by Dock Blaster software using AutoDock 4. Results from this study facilitate the selection of proteins and putative inhibitors for entry into drug design production pipelines.