Rational Drug Designing for Drug Target Alanine Racemase (Alr) of Mycobacterium tuberculosis

Abstract

The emergence of multidrug resistant strains and persistence nature of Mycobacterium tuberculosis has caused stringent need to search novel drug targets. Non-homologous proteins of metabolic pathways are first preference for effective drug designing to avoid the deceptive targeting and side-effect in host parasite diseases. In the present study, fourteen unique pathways have been identified throughin-silico comparative metabolic pathways analysis of the host Homo sapiens and the pathogen M. tuberculosis H37Rv. Alanine Racemase (Rv3423c) was considered for drug designing due its role in cell wall synthesis, cell wall organization , alanine metabolic process , alanine racemase activity, and pyridoxal phosphate binding etc. Alanine Racemase (Alr) has crystallographic structure (1XFC) in Protein Data Bank. Ligand library of 50 molecules were designed through Ligand Scout 2.0 and docking studies were performed by the AutoDock 4.0. On the basis of docking energies, a list of top 6 molecules has been proposed which has good compatibility binding affinity with target. The docking studies also suggest that ASP (85), LYS (156), ALA (181) are important determinant residues in binding with ligands, as they are highly involved in hydrogen bond interactions with the ligands.