In order to artificially expand the genetic information system (AEGIS) and to realize artificial life, it is necessary to discover new functional DNA bases that can form stable duplex DNA and participate in error-free replication. Among the different nucleotides proposed so far, the 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one (P) and 6-amino-5-nitro-2(1H)-pyridone (Z) are found to be promiscuous because of their ability to form stable and unperturbed duplex DNA and participate in error-free replication. Other than P and Z, dNaM and d5SICS were also shown to induce error-free replication. However, occurrences of these nucleotides in DNA are found to destabilize the duplex DNA. By using computer modelling and structural engineering, we have generated various analogues of P, Z, dNaM, and d5SICS, some of which are far more stable than the P:Z and NaM:5SICS base pairs. On the basis of strengths of hydrogen bonding and stacking interactions computed in different sequences, several new nucleobases are proposed to create stable and unperturbed duplex DNA. The electronic environment of these nucleobases also indicates about their possible participation in error-free-replication. As the functionality of a nucleobase is interlinked with its ability to induce mutations, the mutational capabilities of these unnatural nucleobases are also evaluated in detail.

Computational design of unnatural nucleotides for artificial life

2019 Spring National Meeting

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