Title: Potential leads in Tuberculosis management using bioinformatics tools

Biography:

Dr. Namarta Agarwal has completed her MBBS at the age of 27 years from Kathmandu University, Nepal. She is director of Pharmacy in Dr. M C Saxena Group of Colleges.

Abstract

4-hydroxy-tetrahydrodipicolinate synthase (DHDPS) is an important enzyme needed for the biosynthesis of lysine and many more key metabolites in Mycobacterium tuberculosis (Mtb). Inhibition of DHDPS is supposed to a promising therapeutic target due to its specific role in sporulation, cross-linking of the peptidoglycan polymers and biosynthesis of amino acids. In this work, a known inhibitor-based similarity search was carried out against a natural products database (Super Natural II) towards the identification of more potent phyto-inhibitors. Molecular interaction studies were accomplished using three different tools to understand and establish the participation of active site residues as the key players in stabilizing the binding mode of ligands and the target protein. The best phyto-compound deduced on the basis of binding affinity was further used as a template to make similarity scan across the PubChem Compound database (score > = 80 %) to get more diverse leads. In this search, 5098 hits were obtained that further reduced to 262 after drug-likeness filtration. These phytochemicals like compounds were docked at the active site of DHDPS. Then, those hits selected from docking analysis that showing stronger binding and forming maximum H-bonds with the active site residues (Thr54, Thr55, Tyr143, Arg148, and Lys171). Finally, we predicted one phytochemical compound (SN00003544), two PubChem-compounds (CID41032023, CID54025334) akin to phytochemical molecule showing better interactions in comparison of known inhibitors of the target protein. These findings might be further useful to gain structural insight into the designing of novel leads against DapA family.