LAUSR

Proteomic information revealed approximately 3923 proteins in Mycobacterium tuberculosis H37 Rv (M. tuberculosis) genome of which around ∼25% of proteins are hypothetical proteins (HPs). The present work comprises computational approaches to identify and characterize the HPs of M. tuberculosis that symbolize the putative target for rationale development of a drug or anti-tuberculosis strategy. Proteins were primarily classified based on motif and domain information which were further analyzed for the presence of virulence factors, determination of localization and signal peptide/enzymatic cleavage sites. 863 HPs were found, and 599 HPs were finalized based on motifs i.e. GTP (525), Trx (47), SAM (14), PE-PGRS (5) and CBD (8). 80 HPs contain virulence factor, 24 HPs localized in membrane region and four HPs contain signal peptide/enzymatic cleavage sites. The overall parametric study finalizes four HPs Rv0679c, Rv0906, Rv3627c and Rv3811 that also comprise GTPase domain. Structure prediction, structure-based function prediction, molecular docking and mutation analysis of selected proteins were done. Docking studies revealed that GTP and GTPase inhibitor (mac0182344) were docked with all four proteins with high affinities. In silico point mutation studies showed that substitution of aspartate with glycine within a GTPase motif showed the largest decrease in stability and pH differentiation also affect protein's stability. This analysis thus fixes a roadmap in the direction of finding potential target of this bacterium for drug development and enlightens the efficacy of GTP as a major regulator of Mycobacterial cellular pathways. Proteomic information exposed 3923 proteins in Mtb genome of which ∼25% of proteins as hypothetical proteins (HPs). HPs were classified based on the presence of virulence factor, localization, signal peptide/enzymatic cleavage sites. 863 HPs were found that contains GTP (525), Trx (47), SAM (14), PE-PGRS (5) and CBD (8). Rv0679c, Rv0906, Rv3627c and Rv3811 had been shortlisted that also contains GTP binding domains. HPs probably which serves as useful dataset for future studies leading to drug target and TB control of MTB. This article is protected by copyright. All rights reserved.