Riboswitches as Potential Targets for Aminoglycosides Compared with rRNA Molecules: In Silico Study

Abstract

Riboswitches are cis acting riboregulaters in non-coding region of the mRNAs. Their possible contribution in antibiotic targeting especially for FMN, TPP and lysine riboswitches in bacteria has been revealed since a decade ago. Regarding some studies on the possibility of the interaction between aminoglycosides and the artificial riboswitches, in this study we attempted to evaluate the binding potential of different types of aminoglycosides including gentamicin, amikacin, kanamycin, neomycin, tobramaycin, sisomicin and paromomycin with various classes of riboswitches using computational methods. Applying Auto Dock vina, it was shown that the binding energy of each kind of riboswitches with different types of aminoglycosides (riboswitches/aminoglycosides) is almost similar or sometimes more than the binding energy of the aminoglycoside with the corresponding binding cage of “16S rRNA A site” (16S rRNA A site/aminoglycosides) as aminoglycosides’ target site. The affinity between riboswitches and aminoglycosides is almost the same or higher than the affinity of riboswitches/natural ligands. In this study ampicillin was used as the negative control antibiotic and 5S rRNA was employed as the negative control RNA. Results showed that the binding energies of riboswitches/ampicillin and 5S rRNA/aminoglycosides are usually lower than the energy of riboswitches/aminoglycosides. Accordingly, lysine, glycine and SAM-I riboswitches were recognized as the best RNA targets for all of the aminoglycosides because of their higher binding energy. In the next step, docking results were further validated by rDock program. Furthermore, it was shown that hydrogen binding makes a key role in the binding energy between aminoglycosides and riboswitches. Moreover, MD simulation studies on lysine riboswitch/paromomycin complex confirmed the stability of the docked structure in the solvent containing magnesium and chloride ions.