Abstract
To address the structural and dynamical consequences of amino-acid attachment at 2'- or 3'-hydroxyls of the terminal ribose in oligoribonucleotides, we have performed an extensive set of molecular dynamics simulations of model aminoacylated RNA trinucleotides. Our simulations suggest that 3'-modified trinucleotides exhibit higher solvent exposure of the aminoacylester bond and may be more susceptible to hydrolysis than their 2' counterparts. Moreover, we observe an invariant adoption of well-defined collapsed and extended conformations for both stereoisomers. We show that the average conformational preferences of aminoacylated trinucleotides are determined by their nucleotide composition and are fine-tuned by amino-acid attachment. Conversely, solvent exposure of the aminoacylester bond depends on the attachment site, the nature of attached amino acid and the strength of its interactions with the bases. Importantly, aminoacylated CCA trinucleotides display a systematically higher solvent exposure of the aminoacylester bond and a weaker dependence of such exposure on sidechain interactions than other trinucleotides. These features could facilitate hydrolytic release of the amino acid, especially for 3' attachment, and may have contributed to CCA becoming the universal acceptor triplet in tRNAs. Our results provide novel atomistic details about fundamental aspects of biological translation and furnish clues about its primordial origins.