Molecular modeling, simulation and docking of Rv1250 protein from Mycobacterium tuberculosis.

Abstract

Computational prediction and protein structure modeling have come to the aid of various biological problems in determining the structure of proteins. These technologies have revolutionized the biological world of research, allowing scientists and researchers to gain insights into their biological questions and design experimental research much more efficiently. Pathogenic Mycobacterium spp. is known to stay alive within the macrophages of its host. Mycobacterium tuberculosis is an acid-fast bacterium that is the most common cause of tuberculosis and is considered to be the main cause of resistance of tuberculosis as a leading health issue. The genome of Mycobacterium tuberculosis contains more than 4,000 genes, of which the majority are of unknown function. An attempt has been made to computationally model and dock one of its proteins, Rv1250 (MTV006.22), which is considered as an apparent drug-transporter, integral membrane protein, and member of major facilitator superfamily (MFS). The most widely used techniques, i.e., homology modeling, molecular docking, and molecular dynamics (MD) simulation in the field of structural bioinformatics, have been used in the present work to study the behavior of Rv1250 protein from M. tuberculosis. The structure of unknown TB protein, i.e., Rv1250 was retrived using homology modeling with the help of I-TASSER server. Further, one of the sites responsible for infection was identified and docking was done by using the specific Isoniazid ligand which is an inhibitor of this protein. Finally, the stability of protein model and analysis of stable and static interaction between protein and ligand molecular dynamic simulation was performed at 100ns The designing of novel Rv1250 enzyme inhibitors is likely achievable with the use of proposed predicted model, which could be helpful in preventing the pathogenesis caused by M. tuberculosis. Finally, the MD simulation was done to evaluate the stability of the ligand for the specific protein.