Investigations On The Site-preference Of Nucleic Acid Hydrogen Bonding To Quercetin

Exploring binding features between small drug molecule and biomolecule is particularlyimportant because it can provide valuable information for deeply understanding theinteraction mechanism and therefore rationally designing, modifying and screening of newdrugs.In this paper, the site-preference of the nucleic acid bases A, C, G, T and U hydrogenbonding to the small medical molecule quercetin is investigated using the density functionaltheory method. The stable hydrogen-bonded complexes were located at the B3LYP/6-31G(d)level of theory. The binding energies for these complexes were further evaluated at theB3LYP/6-311++G(3df,2p) level of theory with the basis set superposition error corrections.The results indicate that quercetin can interact with uracil or thymine through five bindingsites which herein we refer to as Site qu1, Site qu2, Site qu3, Site qu4, and Site qu5, anduracil (or thymine) can interact with quercetin through three binding sites which herein werefer to as Site u1, Site u2, and Site u3(or Site t1, Site t2, and Site t3). We find that once thebinding site of quercetin is fixed, the hydrogen bonds formed through uracil Site u1orthrough thymine Site t1are the strongest while those formed through uracil Site u2or throughthymine Site t2are the weakest; when the binding site of uracil or thymine is held, thehydrogen bonds formed through quercetin Site qu1are the strongest, those formed throughquercetin Site qu5are the next, while those formed through quercetin Site qu3are the weakest.Quercetin can interact with adenine forming fifteen stable hydrogen-bonded complexes.When the site of querctien is held, the ability of hydrogen bonds formed from N-H of afive-member ring is stronger than the N-H of a six-member ring of the adenine; the hydrogenbonds formed from the lone pair of nitrogen of six-member ring is stronger than the one offive-member ring of the adenine; the hydrogen bond formed through quercetin Site qu1is thestrongest. The atoms in molecules analysis and the natural bond orbital analysis were furthercarried out to explore the interaction natures for these hydrogen-bonded complexes.