title: In silico comparative genomics analysis of Plasmodium falciparum for the identification of putative essential genes and therapeutic candidates.
abstract: 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.
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Orissa, India.
authors.forename: Subhashree
authors.initials: S
authors.lastname: Rout
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: David Charles
authors.initials: DC
authors.lastname: Warhurst
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Orissa, India.
authors.forename: Mrutyunjay
authors.initials: M
authors.lastname: Suar
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Orissa, India. Electronic address: rmahapatra@kiitbiotech.ac.in.
authors.forename: Rajani Kanta
authors.initials: RK
authors.lastname: Mahapatra
mesh_terms: D019295:Computational Biology / Q000379:methods*; D020043:Genes, Essential; D017125:Genes, Protozoan; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010963:Plasmodium falciparum / Q000235:genetics*; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D015800:Protozoan Proteins
keywords: Comparative genomics; Drug targets; Molecular docking; P. falciparum