CH–π interaction between cross-strand amino acid pairs stabilizes β-hairpins

Abstract

We identified several CH–π donor–acceptor pairs involving amino acid side chains with less polarized C–H bonds at a solvent-exposed site between the strands of a β-hairpin peptide. Therein, we observe a distance-dependent induction of CH–π interaction within the aliphatic-aromatic amino acid pair. Our results also suggest an interplay of hydrophobicity and CH–π interaction in dictating the stability of β-hairpins, where a leucine-tryptophan pair contributes −1.14 kcal mol⁻¹ to the overall foldedness of the β-hairpin.