©Innovations in Pharmaceuticals and Pharmacotherapy, All rights reserved Innovations in Pharmaceuticals and Pharmacotherapy www.innpharmacotherapy.com Abstract UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA) is an initial step enzyme, involved in the synthesis of major structural elements (Murein) of bacterial cell wall. MurA shows a similar structural pattern as compared to 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase consisting of two domains encasing catalytic cleft between them. Since crystal structure of Mycobacterium tuberculosis (Mtb-MurA) is not available; therefore, we predicted the three-dimensional (3D) structure using homology modeling approach to understand its detailed structural features. The molecular dynamics (MD) simulations of MurA enzymes from Mycobacterium tuberculosis and Escherichia coli revealed valuable insights into the folding pattern. MD simulation of the Ecoli-MurA and the predicted Mtb-MurA showed similar trajectories and folding patterns. The MurA enzymes remained in their compact and stable state during the 20 ns simulations. Keywords: MurA enzyme; MD simulation; Homology modeling; Molecular docking; E. coli; Protein structure prediction Abbreviations: RMSD, Root Mean Square Deviation; MD, Molecular dynamics; GROMACS, GROningen MAchine for Chemical Simulations; OPLS-AA/L, Optimized Potential for Liquid Simulations/ all atoms; SASA, solvent accessible surface area; PDB, Protein Data Bank. *Corresponding author: Faez Iqbal Khan, Department of Chemistry, Faculty of Applied Science, Durban University of Technology, Durban 4000, South Africa E- mail: khanfaeziqbal@gmail.com 1. Introduction Bacterial cell wall structure and its composition are two essential features required for its survival and growth inside the host [1]. Cell wall is considered as a major target to most of the antibiotics [2]. Murein is a major structural element of the bacterial cell wall formed by the activity of UDP-N- acetylglucosamine 1-carboxyvinyltransferase (MurA, EC 2.5.1.7) enzyme [3]. Murein synthesis is initiated by the transfer of enolpyruvylgroup from phosphoenolpyruvate (pyruvate-P) to the 3-hydroxyl of UDP-N- acetylglucosamine (UDP-GlcNAc) [4]. Escherichia coli MurA (E.coli-MurA) behaves as a potential target for the broad spectrum antibiotic like fosfomycin [5]. MurA is the first enzyme in the synthesis of bacterial cell wall [6]. In a similar way 5-enolpyruvylshikimate-3- phosphate (EPSP) synthase (EC 2.5.1.19) also catalyze a similar reaction and is the sixth enzyme in the shikimate pathway [7]. In contrast to the irreversible inhibition of MurA Research Article A comparative molecular dynamics study of MurA enzymes from E. coli and M. tuberculosis Shahzaib Ahamad 1 , Faez Iqbal Khan 2,* , Urmi Bajpai 3 , Shahnawaz Ali 4 , Neeraja Dwivedi 1 and Md. Imtaiyaz Hassan 4 1 Department of Biotechnology, College of Engineering & Technology, IFTM University, Moradabad, India. 2 Department of Chemistry, Durban University of Technology, Durban-4000, South Africa. 3 Department of Biomedical Sciences, Acharya Narendra Dev College, University of Delhi, India. 4 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India. eISSN: 2321–323X pISSN: 2395-0781