Computational Design of a β-Peptide That Targets Transmembrane Helices

The design of beta-peptide foldamers targeting the transmembrane (TM) domains of complex natural membrane proteins has been a formidable challenge. A series of beta-peptides was designed to stably insert in TM orientations in phospholipid bilayers. Their secondary structures and orientation in the phospholipid bilayer was characterized using biophysical methods. Computational methods were then devised to design a beta-peptide that targeted a TM helix of the integrin alpha(IIb)beta(3). The designed peptide (beta-CHAMP) interacts with the isolated target TM domain of the protein and activates the intact integrin in vitro.