title: Gene network analysis of Aeromonas hydrophila for novel drug target discovery.
abstract: Increasing the multi-drug resistance Aeromonas hydrophila creates a health problem regularly thus, an urgent needs to develop and screen potent antibiotics for controlling of the infections. There are many studies have focused on interactions between specific drugs, little is known about the system properties of a full drug interaction in gene network. Thus, an attractive approach for developing novel antibiotics against DNA gyrase, an enzyme essential for DNA replication, transcription, repair and recombination mechanisms which is important for bacterial growth and cell division. Homology modeling method was used to generate the 3-D structure of B subunit of DNA gyrase (gyrB) using known crystal structure. The active amino acids in 3-D structure of gyrB were targeted for structure based virtual screening of potent drugs by molecular docking. Number of drugs and analogs were selected and used for docking against gryB. The drugs Cinodine I, Cyclothialidine and Novobiocin were found to be more binding affinity with gyrB-drug interaction. The homology of gyrB protein sequence of A. hydrophila resembles with other species of Aeromonas closely showed relationship in phylogenetic tree. We have also demonstrated the gene network interactions of gyrB with other cellular proteins which are playing the key role in gene regulation. These findings provide new insight to understand the 3-D structure of gyrB which can be used in structure-based drug discovery; and development of novel, potent and specific drug against B subunit of DNA gyrase.
authors.affiliation: Institute of Systems and Synthetic Biology, Universite d'Evry Val d'Essonne-Genopole-CNRS UPS3201, Batiment Geneavenir 6, Genopole Campus 1, 5 rue Henri Desbruères, 91030 Evry Cedex, France ; National Bureau of Fish Genetic Resources, Canal Ring Road, PO-Dilkusha, Lucknow, 226002 India.
authors.forename: Vijai
authors.initials: V
authors.lastname: Singh
authors.forename: Dharmendra Kumar
authors.initials: DK
authors.lastname: Chaudhary
authors.forename: Indra
authors.initials: I
authors.lastname: Mani
keywords: Aeromonas hydrophila; Docking; Drug; Gene network; Phylogenetic tree; gyrB