Aromatic interactions in β-hairpin scaffold stability: A historical perspective.

Non-covalent interactions between naturally occurring aromatic residues have been widely exploited as scaffold stabilizing agents in de novo designed peptides and in Nature - inspired structures. Our understanding of the factors driving aromatic interactions and their observed interaction geometries have advanced remarkably with improvements in conventional structural studies, availability of novel molecular methods and in silico studies, which have together provided atomistic information on aromatic interactions and interaction strengths. This review attempts to recapitulate the early advances in our understanding of aromatic interactions as stabilizing agents of peptide β-hairpins.