A very interesting picture emerges from the simulations performed for the systems with alternative RNA monomers. In particular the IpAIpI dinucleotide exhibits a decent pro-portion of WC base pairing interactions with the template, in spite of the formation of only two hydrogen bonds per each I:C pair. We tentatively assign this property to the lower stability of G/O-stacked structures when compared to the systems containing activated A and U nucleotides. Such a preference for the formation of a canonical A-form stack within the IpAIpI dinucleotide could explain its higher binding specificity and fidelity of the process , whereas the reasonable proportion of C3 ′ -endo ribose conformations correlates with the reported high rate of the reaction . This finding for the first time demonstrates that high rate and fidelity of nonenzymatic RNA template copying with nucleotide phosphoroimidazolides is not only modulated by the stability of WC interactions but also by the conformational stability of the canonically stacked quasi-A-form of the imidazolium-bridged dinucleotide intermediate. It is worth noting though that our simulations indicate visibly lower population of IpAIpI fully bound to the template with WC interactions when compared to the GpAIpG dinucleotide. While these results are of high importance for future experimental explorations of this process, more accurate computational data is needed to fully confirm this hypothesis, for example with the support if density functional theory calculations.