Interaction of Adenine Adducts with Thymine: A Computational Study

Abstract

The existence of DNA adducts bring the danger of carcinogenesis because of mispairing with normal DNA bases. 1,N6-ethenoadenine adducts (epsilonA) and 1,N6-ethanoadenine adducts (EA) have been considered as DNA adducts to study the interaction with thymine, as DNA base. Several different stable conformers for each type of adenine adduct with thymine, [epsilonA(1)-T(I), epsilonA(2)-T(I), epsilonA(3)-T(I) and EA(1)-T(I), EA(2)-T(I), EA(3)-T(I)] and [epsilonA(1)-T(II), epsilonA(2)-T(II), epsilonA(3)-T(II) and EA(1)-T(II), EA(2)-T(II), EA(3)-T(II)], have been considered with regard to their interactions. The differences in their geometrical structures, energetic properties, and hydrogen-bonding strengths have also been compared with Watson-Crick adenine-thymine base pair (A-T). Single-point energy calculations at MP2/6-311++G** levels on B3LYP/6-31+G* optimized geometries have also been carried out to better estimate the hydrogen-bonding strengths. The basis set superposition error corrected hydrogen-bonding strength sequence at MP2/6-311++G**//B3LYP/6-31+G* for the most stable complexes is found to be EA(2)-T(I) (15.30 kcal/mol) > EA(1)-T(II) (14.98 kcal/mol) > EA(3)-T(II) (14.68 kcal/mol) > epsilonA(2)-T(I) (14.54 kcal/mol) > epsilonA(3)-T(II) (14.22 kcal/mol) > epsilonA(3)-T(II) (13.64 kcal/mol) > A-T (13.62 kcal/mol). The calculated reaction enthalpy value for epsilonA(2)-T(I) is 10.05 kcal/mol, which is the highest among the etheno adduct-thymine complexes and about 1.55 kcal/mol more than those obtained for Watson-Crick A-T base pair and the reaction enthalpy value for EA(1)- T(II) is 10.22 kcal/mol, which is highest among the ethano addcut-thymine complexes and about 1.72 kcal/mol more than those obtained for Watson-Crick A-T base pair. The aim of this research is to provide fundamental understanding of adenine adduct and thymine interaction at the molecular level and to aid in future experimental studies toward finding the possible cause of DNA damage.