Tetraloop-like Geometries Could Form the Basis of the Catalytic Activity of the Most Ancient Ribooligonucleotides

The origin of the catalytic activity of ancient oligonucleotides is a largely unexplored field of contemporary science. In the current work we use molecular dynamics simulations to investigate the plausibility of tetraloop-like overhang geometries to initiate transphosphorylation reactions that lead to ligation and terminal cleavage in simple, Watson–Crick (WC) complementary oligoC/oligoG sequences observed experimentally. We show a series of examples of known tetraloop architectures, which can be adopted by the unpaired overhangs of short oligonucleotide sequences for a sufficiently long time to enable chemical reactions that lead to simple ribozyme-like catalytic activity. Thus, our computations demonstrate that the role of non-WC interactions at the emergence of the most ancient catalytic oligonucleotides could be more significant than ever believed