Classification and functional analyses of putative virulence factors of Mycobacterium tuberculosis: A combined sequence and structure based study

Mohd Shahbaaz; Vladimir Potemkin; Krishna Bisetty; Md Imtaiyaz Hassan; Mostafa A Hussien

doi:10.1016/j.compbiolchem.2020.107270

Classification and functional analyses of putative virulence factors of Mycobacterium tuberculosis: A combined sequence and structure based study

Comput Biol Chem. 2020 May 5:87:107270. doi: 10.1016/j.compbiolchem.2020.107270. Online ahead of print.

Authors

Mohd Shahbaaz¹, Vladimir Potemkin², Krishna Bisetty³, Md Imtaiyaz Hassan⁴, Mostafa A Hussien⁵

Affiliations

¹ South African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute (SANBI), University of the Western Cape, Private Bag X17, Bellville 7535, Cape Town, South Africa; Laboratory of Computational Modeling of Drugs, South Ural State University, 76 Lenin prospekt, 454080 Chelyabinsk, Russia.
² Laboratory of Computational Modeling of Drugs, South Ural State University, 76 Lenin prospekt, 454080 Chelyabinsk, Russia.
³ Department of Chemistry, Durban University of Technology, Durban, 4000, South Africa.
⁴ Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
⁵ Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203 Jeddah 21589, Saudi Arabia; Department of Chemistry, Faculty of Science, Port Said University, Port Said, 42521, Egypt.

PMID: 32438116
DOI: 10.1016/j.compbiolchem.2020.107270

Abstract

The emergence of the drug-resistant mechanisms in Mycobacterium tuberculosis poses the biggest challenges to the current therapeutic measures, which necessitates the identification of new drug targets. The Hypothetical Proteins (HPs), a class of functionally uncharacterized proteins, may provide a new class of undiscovered therapeutic targets. The genome of M. tuberculosis contains 1000 HPs with their sequences were analyzed using a variety of bioinformatics tools and the functional annotations were performed. The functions of 662 HPs were successfully predicted and further classified 483 HPs as enzymes, 141 HPs were predicted to be involved in the diverse cellular mechanisms and 38 HPs may function as transporters and carriers proteins. Furthermore, 28 HPs were predicted to be virulent in nature. Amongst them, the HP P95201, HP P9WM79, HP I6WZ30, HP I6 × 9T8, HP P9WKP3, and HP P9WK89 showed the highest virulence scores. Therefore, these proteins were subjected to extensive structure analyses and dynamics of their conformations were investigated using the principles of molecular dynamics simulations, each for a 150 ns time scale. This study provides a deeper understanding of the undiscovered drug targets and the generated outputs will facilitate the process of drug design and discovery against the infection of M. tuberculosis.

Keywords: Hypothetical proteins; Molecular dynamics simulations; Mycobacterium tuberculosis; Sequence analyses; Structure analyses; Virulence factors.