Theoretical Study Of The Noncovalent Interactions Between Kanamycin A And Bases

Studying the noncovalent interactions between aminoglycoside antibiotics and RNA bases is very important for understanding the recognition mechanism,developing and designing new antibacterial drugs effectively.In this work,33 hydrogen-bonded complexes and 4 stacked complexes formed by kanamycin A and 4 RNA bases were selected.For hydrogen-bonded complexes,B3LYP/6-31+G(d,p)method is used to optimize the structures;M06-2X-D3/aug-cc-p VDZ method is used to calculate gas phase interaction energy,interaction energy between water environment and protein environment under PCM model,and the atoms in molecules(AIM),natural bond orbital(NBO)analysis and the calculation of a single hydrogen bond energy in the complexes.M06-2X/6-31+G(d,p)method is used to determine the stable structure of the stacked complexes.The details are as follows:1.Hydrogen bonding(1)The potential hydrogen bonding sites between kanamycin A and four bases were explored.The results showed that kanamycin A tendeds to form more stable hydrogen-bonded complexes with bases at K3 site;adenine,guanine,uracil and cytosine tends to form hydrogen-bonded complexes with kanamycin A at A3,G3,U3 and C2 sites,respectively.(2)Comparing to phase interaction,the interaction in water environment and protein environment was weaker,but magnitude was basically consistent with the results in gas phase.(3)The results showed that the order of the kanamycin A hydrogen bonding sites stability derived from the protonation and deprotonation reaction enthalpy values and derived from the MK charge is consistent with the order of stability of the interaction energy.2.StackingThe results of interaction energy of the stacked complexes showed that the magnitudeorder of the four bases that stacks with kanamycin A: guanine G > adenine A > cytosine C >uracil U.Kanamycin A is more likely to form hydrogen bonding with four bases than stacking.