De novo design and structural analysis of a model beta-hairpin peptide system

We have designed de novo a simple, context-free, model linear peptide system to fold into a regular beta-hairpin structure, with three-residue beta-strands connected by a type I' beta-turn. CD and NMR analysis of this peptide in aqueous solution show that the peptide folds into the expected conformation. Structural characterization of three peptide variants, in which some of the strand side-chains have been substituted by alanine, demonstrates that inter-strand side chain-side chain interactions are essential for beta-hairpin formation. This simple model system will help to isolate the factors behind beta-sheet formation, and contribute useful information about de novo protein design.