Helix is a helix is a helix?

The experimental approach has been to perform “host–guest” experiments in which the effect of individually substituting each “guest” amino acid on the stability of a “host” protein or peptide is measured. As a result of such studies, a quantitative ranking of the propensity of each amino acid to adopt a α-helical or β-sheet conformation is obtained (3, 4). Of key importance is the selection of the host protein or peptide and the local environment of the guest site. If such measurements are to be meaningful the aim, in so far as it is experimentally feasible, is to isolate the guest site from interactions with neighboring residues. The goal is to measure only the free energy associated with the unfolded-to-helix transition. To date, several different hosts have been employed, initially block copolymers (5) and more recently short, designed peptides (6–9) and small natural proteins (10 …