Identification of ligand binding activity and DNA recognition by RhlR protein from opportunistic pathogen Pseudomonas aeruginosa —a molecular dynamic simulation approach

Abstract RhlR protein from opportunistic pathogen Pseudomonas aeruginosa is involved in the transcription of virulence genes of the organism. The RhlR protein functions as a dimer and binds to the cognate promoter DNA with the help of an autoinducer ligand BHL to initiate the transcription of the virulence genes. Till date, there are no reports that detail the mechanism of virulence gene expression by RhlR protein in P. aeruginosa . In this work, we tried to analyse the molecular aspects of the various binding interactions of the RhlR protein while formimg the dimmer as well as with the promoter DNA. We analysed the mode of dimerisation of the RhlR protein and its binding interactions with the autoinducer BHL ligand. From our analyses, we could identify the potential amino acid residues which are involved in the binding interactions. We also predicted how the autoinducer BHL would help in making contacts with the DNA as well as with itself. Thus, the autoinducer BHL would serve as an important mediator of molecular interactions involved in binding the RhlR protein to itself as well as with the promoter DNA. Therefore, any other molecule which would be able to compete with the autoinducer ligand BHL to bind to RhlR protein but would not let the RhlR protein bind the promoter DNA would be an ideal drug candidate to prevent the transcription process of the virulence genes in P. aeruginosa . Our future aim is to predict suitable ligands which would compete with BHL to thwart the transcription process.