Hydrogen-Bonding Strengths in Pyrrolidinyl Peptide Nucleic Acid and DNA Base Pairs: A Density Functional Theory (DFT) Study

Abstract

The H-bond strengths of the single base pair formed from Pyrrolidinyl Peptide Nucleic Acid (PNA) and charged as well as neutral Deoxyribonucleic Acid (DNA) were studied using the density functional theory. The B3LYP/6-31+G(d,p) level of theory was employed for evaluating the binding energies and structural parameters of heterogeneous and homogeneous base pairs. The strongest H-bond strengths were obtained from the heterogeneous base pairs, yielding the binding energies of −29.9 and −18.9 kcal/mol for the PNA-GC-DNA and PNA-AT-DNA base pairs, respectively. In contrast, a dramatic change on the H-bond strengths was observed from the charged homogenous base pairs with the binding energies of −6.2 and +10.2 kcal/mol for the DNA-GC-DNA and DNA-AT-DNA base pairs, respectively. With the neutralization of negative charges in the DNA backbone, the corresponding values of −29.1 and −11.7 kcal/mol were elucidated from the Na-DNA-GC-DNA-Na and Na-DNA-AT-DNA-Na base pairs, respectively, proving that the repulsion between two negative charges in the phosphate backbone plays a significant role to the H-bond interactions in base pairs. In addition, a high specificity and preferential binding between the pyrrolidinyl PNA and DNA base pairs were also observed.