title: Computational identification of potent inhibitors for Streptomycin 3″-adenylyltransferase of Serratia marcescens.
abstract: Serratia marcescens is an opportunistic pathogen responsible for the respiratory and urinary tract infections in humans. The antibiotic resistance mechanism of S. marcescens is mediated through aminoglycoside modification enzyme that transfer adenyl group from substrate to antibiotic through regiospecific transfers for the inactivation of antibiotics. Streptomycin 3″-adenylyltransferase acts on the 3' position of the antibiotic and considered as a novel drug target to overcome bacterial antibiotic resistance. Till now, there is no experimentally solved crystal structure of Streptomycin 3″-adenylyltransferase in S. marcescens. Hence, the present study was initiated to construct the three dimensional structure of Streptomycin 3″-adenylyltransferase in order to understand the binding mechanism. The modeled structure was subjected to structure-based virtual screening to identify potent compounds from the five chemical structure databases. Furthermore, different computational methods such as molecular docking, molecular dynamics simulations, ADME toxicity assessment, free energy and density functional theory calculations predicted the structural, binding and pharmacokinetic properties of the best five compounds. Overall, the results suggested that stable binding confirmation of the five potent compounds were mediated through hydrophobic, π-π stacking, salt bridges and hydrogen bond interactions. The identified compounds could pave way for the development of anti-pathogenic agents as potential drug entities.
authors.affiliation: Department of Bioinformatics, Alagappa University, Science Campus, Karaikudi 630004, Tamil Nadu, India.
authors.forename: Dhamodharan
authors.initials: D
authors.lastname: Prabhu
authors.affiliation: Department of Bioinformatics, Alagappa University, Science Campus, Karaikudi 630004, Tamil Nadu, India.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Vidhyavathi
authors.affiliation: Department of Bioinformatics, Alagappa University, Science Campus, Karaikudi 630004, Tamil Nadu, India. Electronic address: jjkanthan@gmail.com.
authors.forename: Jeyaraman
authors.initials: J
authors.lastname: Jeyakanthan
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D012706:Serratia marcescens / Q000201:enzymology*
chemical_list: D000900:Anti-Bacterial Agents; D008024:Ligands; D009713:Nucleotidyltransferases; C022678:streptomycin 3''-adenylyltransferase
keywords: Density functional theory and molecular dynamics simulation; Homology modeling; Serratia marcescens; Structure-based virtual screening