Disrupting Helix Formation in Unsolvated Peptides

Protonated polyalanine peptides form helices in the gas phase when their most basic protonation site (the N-terminus) is blocked by acetylation: Ac-A n +H + (Ac = acetyl and A = alanine). The glycine analogues, Ac-G n +H + ( G = glycine), on the other hand, form random globules. The disruption of helix formation in unsolvated Ac-A n G x A m +H + peptides has been examined as a function of n + m, and x using high resolution ion mobility measurements and molecular dynamics simulations. A surprisingly large block of glycine residues is required to disrupt helix formation in these peptides. For example, Ac-A 5 G 3 A 5 +H + and Ac-A 6 G 5 A 6 +H + both remain helical at room temperature. According to molecular dynamics simulations, the glycines do not cause a localized disruption of the helices, as might be expected for a residue considered a helix breaker. This is consistent with helix disruption occurring through a global effect on the relative energies of the helix and globule rather than through a localized entropic effect.