Molecular modeling of the selectivity in artificial DNA base pairs

Abstract

DNA is the code of life. The idea of being able to modify this essential molecule for life has aroused the interest of many researchers in recent years due to the wide range of possibilities that can be considered. This work can be defined as a first approximation to one of the great challenges we face in addressing this issue, the selectivity in DNA replication, which is directly influenced by the stability of the base pairs incorporated in the double helix of DNA. This work includes a bibliographic review of the different strategies used in the design of artificial DNA base pairs, focusing mainly on their structures and their evolution until reaching selectivity values close to those of natural base pairs. In addition, this work includes a computational study on the predominant non-covalent interactions in these systems (hydrogen bonding and π-π stacking interactions) of a total set of 10 base pairs, including the two Watson-Crick base pairs and eight artificial DNA base pairs, four hydrogen-bonded and four non-hydrogen-bonded. From this study, the level of importance of both interactions in the total stability, as well as the different factors contributing to them, has been demonstrated. On the one hand, it has been demonstrated that hydrogen bonding interactions are predominant in the case of hydrogen-bonded artificial DNA base pairs. In this type of interaction, a significant covalent component has been identified. Additionally, the correlation between charge accumulation in monomers and the strength of hydrogen bonds has been demonstrated. Moreover, it has been demonstrated that for the case of non-hydrogen-bonded artificial DNA base pairs, π-π stacking interactions are predominant, and they are determinant towards the incorporation of such unnatural base pairs in DNA helix. Despite the absence of hydrogen bonds, non-null interactions between bases have also been identified in these base pairs. Furthermore, it has been demonstrated how cross interactions play a significant role in π-π stacking interactions, sometimes becoming more important than stacking between bases in certain systems. Finally, within π-π stacking interactions, an additional interaction, cooperativity, has been identified.