ChemSystemsChem, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Abstract Nonenzymatic self‐replication is considered as one of the most primordial functions RNA, which likely preceded emergence more complex ribozymes. Among different possible scenarios, nucleotide activation with imidazole derivatives attracted substantial attention over last years. However, despite progress in proposing plausible variants nonenzymatic RNA template copying phosphoroimidazolides, mechanistic aspects this process still remain obscure. Furthermore, efficient involving activated uridine and adenosine remains a challenge. Here, we employed classical molecular dynamics simulations to evaluate binding specificity imidazolium‐bridged dinucleotide intermediates, was suggested control yield fidelity reaction. In particular, RMSD‐based clustering MD trajectories revealed previously unknown structural arrangements intermediates that may play critical role primer extension. Most importantly, our results indicate cannot be simply associated number Watson–Crick hydrogen bonds between dinucleotides templating strand. Instead, efficiency reaction correlates preference for formation canonically stacked form intermediate, can then selectively bind participate extension

Language: Английский