title: Molecular modeling, simulation and virtual screening of MurD ligase protein from Salmonella typhimurium LT2.
abstract: The Mur enzymes of the peptidoglycan biosynthesis pathway constitute ideal targets for the design of new classes of antimicrobial inhibitors in Gram-negative bacteria. We built a homology model of MurD of Salmonella typhimurium LT2 using MODELLER (9v12) software. 'The homology model was subjected to energy minimization by molecular dynamics (MD) simulation study with GROMACS software for a simulation time of 20 ns in water environment. The model was subjected for virtual screening study from the Zinc Database using Dockblaster software. Inhibition assay for the best inhibitor, 3-(amino methyl)-n-(4-methoxyphenyl) aniline, by flow cytometric analysis revealed the effective inhibition of peptidoglycan biosynthesis. Results from this study provide new insights for the molecular understanding and development of new antibacterial drugs against the pathogen.
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India.
authors.forename: Himanshu Bhusan
authors.initials: HB
authors.lastname: Samal
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India.
authors.forename: Jugal Kishore
authors.initials: JK
authors.lastname: Das
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India. Electronic address: rmahapatra@kiitbiotech.ac.in.
authors.forename: Rajani Kanta
authors.initials: RK
authors.lastname: Mahapatra
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India. Electronic address: msuar@kiitbiotech.ac.in.
authors.forename: Mrutyunjay
authors.initials: M
authors.lastname: Suar
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005820:Genetic Testing / Q000379:methods*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics*; D017433:Protein Structure, Secondary; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D010453:Peptide Synthases; C053379:UDP-N-acetylmuramoylalanine-D-glutamate ligase
keywords: Docking; Molecular dynamics; MurD ligase; Salmonella typhimurium LT2; Virtual screening