Determination of murG Transferase as a Potential Drug Target in Neisseria meningitides by Spectral Graph Theory Approach

Abstract

The Neisseria meningitides has overcome the several front line drugs, which inhibit penicillin binding protein synthesis and develop resistance or tolerance to these drugs. To overcome this situation, here we have attempted to reconstruct the metabolic network of peptidoglycan biosynthesis pathway of Neisseria meningitides, to obtain the potential drug target other than the penicillin binding proteins, as the biological networks like transcriptional, gene regulatory, metabolic or protein-protein interaction networks of organisms are widely studied, giving an insight into metabolism and regulation. The metabolic network was constructed based on the KEGG database, followed by graph spectral analysis of the network to identify hubs as well as sub-clustering of the reactions. Analysis of the eigen values and spectrum of the normalized laplacian matrix of the reaction pathway indicate the enzyme, murG transferase, catalyzing N-acetylglucosamine (GlcNAc) may considered as a potential drug target. As a case study, we have built a homology model of identified drug target murG transferase and various information have been generated through molecular dynamics, which will be useful in wetlab structure determination. The three-dimensional (3D) structure is essential for functional annotation and rational drug design. Accurate models are suitable for a wide range of applications, such as prediction of protein binding sites, prediction of the effect of protein mutations, and structure-guided virtual screening. The generated model can be further explored for insilico docking studies with suitable inhibitors.