Association of aminoglycosidic antibiotics with the ribosomal A-site studied with Brownian dynamics. Journal of chemical theory and computation [J Chem Theory Comput] Journal article

Brownian dynamics methodology was applied to simulate the encounter of aminoglycosidic antibiotics with the ribosomal A-site RNA. Studied antibiotics included neamine, neomycin, ribostamycin and paromomycin which differ in chemical structure, the number of pseudo-sugar rings and the net charge. The influence of structural, electrostatic and hydrodynamic properties of antibiotics on the kinetics of their association with the ribosomal A-site was analyzed. The computed diffusion limited rates of association are of the order of 10(10)1Ms and they weakly depend on ionic strength. Prior to binding antibiotics often slide along the RNA groove with the time scale of approximately 10 ns per base pair in case of neamine. We observed that upon forming the encounter complex aminoglycosides displace from the binding pocket up to two Mg(2+) ions.

Journal of chemical theory and computation [J Chem Theory Comput]