Helix-turn-helix motifs in unsolvated peptides

The conformations of unsolvated Ac-A14KG3A14K + 2H+ (Ac = acetyl, A = alanine, K = lysine, G = glycine) have been examined by ion mobility measurements and molecular dynamics simulations. This peptide was designed as a model helix-turn-helix motif. It was found to adopt three distinct geometries which were assigned to an extended helical conformation which is only stable at low temperatures (<230 K), a relatively high energy but metastable structure with exchanged lysines, and a coiled-coil. The coiled coil (which consists of an antiparallel arrangement of two helical alanine sections linked by a flexible glycine loop) is the dominant conformation. For temperatures >350 K, the experimental results indicate the helices uncouple and the loop randomizes. From equilibrium constants determined for this helix coupling ⇄ uncoupling transition, we found ΔH° = -45 kJ mol-1 and ΔS° = 114 J K-1 mol-1. -ΔH° is essentially the enthalpy change for docking the two helices together while ΔS° is essentially the entropy change for freeing up the glycine loop. Copyright © 2003 American Chemical Society.