Abstract

DESIGNING OF POTENTIAL DRUG-LIKE INHIBITORS TO SERINE-THREONINE PROTEIN KINASE B (PKNB) IN TUBERCULOSIS THROUGH COMPUTER-AIDED DRUG DESIGN

Wagh Jyoti. Gorakh*., Sandip Sachan, Dharmendra Ahuja, Banerjee Angshu

Abstract

The emergence of multidrug-resistance strains of Mycobacterium tuberculosis has intensified efforts to discover novel drugs for tuberculosis treatment. Targeting the persistant state of Mycobacterium tuberculosis, in which Mycobacterium tuberculosis is resistant to conventional drug therapies, is of particular interest. PknB is most important protein kinases in causing tub erculosis disease. This protein has also some variation, two threonine residues in the activation loop, found in the mostly disordered in the crystal structure of this kinase, namely Thr171 and Thr173, were identified as the target for PknB autophosphorylation.It is a functional kinase i.e. autophosphorylation on serine- threonine residue and also able to phosphorylates the peptide substrates. GarA plays direct role in causing tuberculosis disease. The main aim of this project is to design a potent drug against ‘catalytic/protein kinase domain’ of trans-membrane signaling enzyme ‘eukaryotic like-Serine-threonine protein kinase B’ (PknB) from Mycobacterium tuberculosis by ‘molecular docking approach’. In this, 50 drugs designed and screened against PknB as receptor based on the lowest energy with repeated conformation of ligands and, passed through ADME/TOPKAT toxicity prediction to sort out the toxic compounds. Then 10 drugs were selected which were not toxic and docked with the PknB receptor protein. Binding

Keywords: Docking, Kinase, Tuberculosis, Proteins, Ligand, Sequence analysis etc.