Bacterial ribosomal RNA is a target for many antibiotics. For example, aminoglycoside antibiotics bind to one of the tRNA binding sites (the A-site) in the small ribosomal subunit. Aminoglycoside binding decreases the flexibility of two adenines responsible for the fidelity of translation, which results in the production of dysfunctional proteins.We investigate the interactions of various compounds with the ribosomal A-site RNA. We also study how nucleotide substitutions affect the physicochemical properties of the A-site since the mutations in the target RNA are one of the causes of bacterial resistance. The structural and thermodynamic properties of the complexes are derived from computational modeling (molecular dynamics, Poisson-Boltzmann model) and experimental measurements (fluorescence and absorbance spectroscopy and isothermal titration calorimetry). We also perform growth inhibition checks on bacteria and cell-free translation systems.

Targeting bacterial ribosomal RNA

243rd National Meeting (2012)

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