Principles of amino-acid–ribonucleotide interaction revealed by binding affinities between homogeneous oligopeptides and single-stranded RNA molecules

We have determined the binding strengths between ribonucleotides of adenine (A), guanine (G), uracil (U), and cytosine (C) in homogeneous single-stranded ribonucleic acids (ssRNAs) and homo-decapeptides consisting of 20 common amino acids. We use a bead-based fluorescence assay for these measurements in which decapeptides are immobilized on the bead surface and ssRNAs are in solutions. The results provide a molecular basis for analyzing selectivity, specificity, and polymorphisms of amino-acid–ribonucleotide interactions. Comparative analyses of the distribution of the binding energies reveal unique binding strength patterns assignable to each pair of amino acid and ribonucleotide originating from the chemical structures. Pronounced favorable (such as Arg–G) and unfavorable (such as Met–U) binding interactions can be identified in selected groups of amino acid and ribonucleotide pairs that could provide basis to elucidate energetics of amino-acid–ribonucleotide interactions. Such interaction selectivity, specificity, and polymorphism manifest the contributions from RNA backbone, RNA bases, as well as main chain and side chain of the amino acids. Such characteristics in peptide–RNA interactions might be helpful for understanding the mechanism of protein–RNA specific recognition and the design of RNA nano-delivery systems based on peptides and their derivatives.