Folding and unfolding of helix-turn-helix motifs in the gas phase

Abstract

Ion mobility measurements and molecular dynamic simulations have been performed for a series of peptides designed to have helix-turn-helix motifs. For peptides with two helical sections linked by a short loop region: AcA14KG3A14K+2H+, AcA14KG5A14K+2H+, AcA14KG7A14K+2H+, and AcA14KSar3A14K+2H+ (Ac = acetyl, A = alanine, G = glycine, Sar = sarcosine and K = lysine); a coiled-coil geometry with two anti-parallel helices is the lowest energy conformation. The helices uncouple and the coiled-coil unfolds as the temperature is raised. Equilibrium constants determined as a function of temperature yield enthalpy and entropy changes for the unfolding of the coiled-coil. The enthalpy and entropy changes depend on the length and nature of the loop region. For a peptide with three helical sections: protonated AcA14KG3A14KG3A14K; a coiled-coil bundle with three helices side-by-side is substantially less stable than a geometry with two helices in an antiparallel coiled-coil and the third helix collinear with one of the other two.