Theoretical characterization of the conformational features of unnatural oligonucleotides containing a six nucleotide genetic alphabet.

ABSTRACT

The addition of the unnatural PZ base pair to the four naturally occurring DNA bases expands the genetic alphabet and yields an artificially expanded genetic information system (AEGIS). Herein, the structural feature of oligonucleotides containing a novel unnatural PZ base pair is characterized using both molecular dynamics and quantum chemistry. The results show that the incorporation of the novel artificial base pair (PZ) preserves the global conformational feature of duplex DNA except for some local structures. The Z-nitro group imparts new properties to the groove width, which widens the major groove. The unnatural oligonucleotides containing mismatched base pairs exhibit low stability. This ensures efficient and high-fidelity replication. In general, the incorporation of the PZ pair strengthens the stability of the corresponding DNA duplex. The calculated results also show that the thermostability originates from both hydrogen interaction and stacking interaction. The Z-nitro group plays an important role in enhancing the stability of the H-bonds and stacking strength of the PZ pair. Overall, the present results provide theoretical insights in the exploration of artificially expanded genetic information systems.