In silico studies for potential natural inhibitors for isocitrate dehydrogenase type II of mycobacterium tuberculosis (H37Rv)

Abstract

Background and Objective: Tuberculosis is a life threatening bacterial disease caused by Mycobacterium tuberculosis (M. tuberculosis) which has affected the population of almost all parts of the world since time immemorial. Although remarkable discovery has been achieved in combating disease control and its propagation but due to emergence of resistant strain of M. tuberculosis exhaustive search for the panacea to counter the bacteria is still on. This study proposes in silico studies of 35 natural compounds against proposed drug target isocitrate dehydrogenase type II (PDBID: 5 KVU) of M. tuberculosis (H37Rv). Almost all available antitubercular drugs in the market now-a-days have some side effects. Hence, there is a strong need of some natural antitubercular compounds that can mitigate the side effects and boost up the overall health of the patients. The aim of the present study was to explore the potential novel natural inhibitor against proposed drug target, isocitrate dehydrogenase II. Materials and Methods: Crystal structure of isocitrate dehydrogenase II was obtained from PDB. All natural compounds used in this study were obtained from Pubchem database and their drug likeliness was also crosschecked. Docking studies were performed with the help of Autodock 4.0. NADP+ was used as a reference ligand to compare the docking results with natural compounds. Molecular dynamics study of the docked complex has also been performed to infer the deep insight of the various interactions and stability of the receptor-ligand docked complex. Results: Results showed that molecular docking of isocitrate dehydrogenase II of M. tuberculosis against all 35 natural multi-beneficial compounds, Amentoflavone attained the minimum binding energy, hence amentoflavone is most potential natural compound that may inhibit the proposed enzyme. The molecular dynamics study of the docked receptor ligand complex also showed good congruence to the docking result. Conclusion: Natural compounds showed good binding energies with the receptor protein isocitrate dihydogenase II and amentoflavone, a natural ligand may act as a strong anti-tubercular lead compound against M. tuberculosis.