Design of molecular inhibitors against the NuoC protein of Mycobacterium tuberculosis.

Abstract

Tuberculosis (TB) is one of the main health issues for the international scientific community. The NADH- quinone oxidoreductase subunit C (NuoC) protein belongs to the NADH dehydrogenase family, which plays a critical role in the electron transport chain and ATP synthesis and energy production in Mycobacterium tuberculosis (Mtb). In the present study, Nuoc protein is considered a potential drug target for identifying inhibitors for the protein. The Nuoc protein’s 3D structural features are determined using computational techniques, including active site identification, ADME properties and virtual screening. The NuoC theoretical model was developed using homology modeling techniques and its structure was verified by various validation methods. They provide insight into the conformational changes occurring in the NuoC protein. To identify drug-like compounds virtual screening studies were conducted around the active site using several ligand databases. According to the research residues the amino acid residues ARG98, ARG75 (basic), ASP99, ASP189, ASP98 (acidic), LEU101, LEU194 (nonpolar neutral), THR180 (polar neutral), GLU177(polar neutral), TYR181(polar neutral), PRO102, PRO192 (nonpolar neutral), and HIS191(basic) are important in drug-target interactions. Additionally, docking experiments of TB medications against NuoC were carried out. The study found that the ADME parameters of the selected ligand molecules are more favourable compared to existing TB drugs. This highlights the drug-like activity of the ligand molecules in inhibiting NuoC proteins. The structural data, along with the information about the active site and the selected ligand molecules, can help in identifying new therapeutic scaffolds for the treatment of Tuberculosis.