A molecular dynamics study on binding recognition between several 4,5 and 4,6-linked aminoglycosides with A-site RNA

A molecular dynamics (MD) simulation has been performed for two sets of aminoglycoside antibiotics bound with an RNA duplex corresponding to the aminoacyl-tRNA decoding site of the 16S rRNA to characterize the energetics and dynamics of binding for several aminoglycosides. The binding free energy, essential dynamics and hydration analysis have been conducted to characterize the dynamics' properties associated with the binding recognition between each set of antibiotics and the RNA duplex. We have built several dynamic models with reasonable binding free energies showing good correlation with the experimental data. We have also conducted a hydration analysis on some long residency water molecules detected as W8 and W49 sites around the U1406 . U1495 pair and which are found to be important in binding recognition and in causing some apparent stretch variations of this pair during the dynamic studies. In addition, we also find that the hydration sites with long residence time identified between the ring III of two 4,6-linked antibiotics (tobramycin and kanamycin) and phosphate oxygen atoms of G1405/U1406 may be worthy of further exploration for rational drug design.