Accurate Base Pair Energies of Artificially Expanded Genetic Information Systems (AEGIS): Clues for Their Mutagenic Characteristics

Recently, several artificial nucleobases, such as B, S, J, V, X, K, P, and Z were proposed to help in the expansion of the genetic information system and diagnosis of diseases. Among these bases, P and Z were identified to form stable DNA and to participate in the replication. However, the stabilities of P:Z and other artificial base pairs are not fully understood. The abilities of these unnatural nucleobases in mispairing with themselves and with natural bases are also not known. Here, the B97X-D dispersion-corrected density functional theoretical and complete basis set (CBS-QB3) methods are used to obtain accurate structural and energetic data related to base pair interactions involving these unnatural nucleobases. The roles of protonation and deprotonation of certain artificial bases in inducing mutations are also studied. It is found that each artificial purine has a complementary artificial pyrimidine, the base pair interactions between which are similar to those of the natural Watson-Crick base pai...