Thermodynamic Stability of Stereoisomeric Lactam and benzo[a]pyrene Derivatives in a DNA Mutation

The progression of oxidation which occurs during the enzymatic metabolism from benzo[a]pyrene to BPDE causes the alteration of the structure and the abnormal replication proceeds to gene mutation. Density-functional theory and quantum mechanical modelling techniques were used to study electronic structure of stereoisomeric lactam and benzo[a]pyrene(BP) derivatives in a DNA Mutation. In the process of intercalation which results in the formation of an adduct through binding with guanine bases in the DNA, thermodynamic changes were observed while the lactam and BP intercalates to form an adduct. We performed a computational analysis to uncover the structural and thermodynamic changes during the intercalation using molecular dynamics simulation. The free energy differences and the differences in thermodynamic stability between the stereoisomeric adducts were observed during the reaction.