VAWKUM Transactions on Computer Sciences http://vfast.org/journals/index.php/VTCS@ 2016, ISSN(e):2308-8168, ISSN(p): 2411-6335 Volume 10, Number 2, July-August, 2016 pp. 01–-07 COMPUTATIONAL APPROACH TO DESIGN ANTAGONISTS OF MYCOBACTERIUM TUBERCULOSIS LIPOPROTEIN LPRG (RV1411C) PROTEIN ASIF HASSAN SYED* 1 , TABREJ KHAN 2 , ARSHAD HASHMI 2 ` 1 Department of Computer Science, Faculty of Computing and Information Technology, Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia 2 Department of Information Systems, Faculty of Computing and Information Technology, Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia Email: shassan1@kau.edu.sa Received June 2016, Revised August 2016 ABSTRACT. Evolution of multi-drug resistance strains of Mycobacterium tuberculosis (MTB) has in the past caused severe epidemics of tuberculosis across the globe thereby it raises a question on the potency or efficacy of the current scaffolds of drugs targeting MTB. Therefore, there an urgency to identify novel antimycobacterial compounds targeting proteins important for the viability of Multi-Drug-Resistant Tuberculosis (MDR-TB) strains. In this regard, Mtb LprG (Rv1411c) a lipoprotein involved in the elusion of cell-mediated immune response within infected host macrophages, is an important target for screening antimycobacterial compounds against Mtb. In the current study, a workflow comprising of virtual screening of ligand using USRCAT (Ultra Shape Recognition) and molecular docking protocols were employed to identify novel antituberculosis compounds. Based on USRCAT and docking studies XPX an analog of triacylated glycolipid was screened as a promising lead molecule that shows higher specificity and binding affinity for Mtb LprG protein. Further, in vitro experimentations are required to testify the role of XPX as an anti-TB drug for the treatment of MDT-TB. Keywords: Multi-drug Resistant Tuberculosis; Toll-like receptor 2 (TLR2); antagonist; Molecular docking; Virtual screening 1. Introduction. Tuberculosis (TB) a highly infectious disease which continues to cause an alarming toll on a human being worldwide. In 2012, there were around 8.6 million TB cases were reported and the casualty 1.3 million approximately. Among these deaths, there were an estimated 170000 from Multidrug-Resistance Tuberculosis (MDR-TB), a relatively high total compared with 45000 cases of MDR-TB [1]. In this context, research effort to identify novel target specific antituberculosis compounds against diverse strains of M. tuberculosis is an important step in combating the growing menace of MDR strains of Mycobacterium tuberculosis across the globe [2]. LprG (Rv1411c) lipoprotein is involved in the TLR2 depended on evasion of immune responses with host macrophages. The LprG protein acts as an agonist for TLR2 receptor protein and the efficacy of the TLR2-LprG interaction is enhanced by the formation of an intermediate complex between the LprG and triacylated glycolipids. The triacylated glycolipid binds precisely at the hydrophobic residues lining the cavity of H37Rv-LprG protein. The finding of a triacylated glycolipid in the hydrophobic pocket of LprG protein has vital effects on the role of LprG protein in the survival, persistence, and physiology of MTB in the host macrophages [3]. The encoding of p55 (Rv1410c) and LprG (Rv1411c) in a particular operon are significant for virulence [4-6]. Prolonged exposure of more than 16 h of human macrophages to H37Rv-LprG lipoprotein (TLR2 receptor acylated agonist) results in visible inhibition of MHC-II Ag processing. Furthermore, MHC-II Ag processing inhibition by H37Rv-LprG lipoproteins may permit survival of MTB within infected 1