Stabilizing α-Helicity of a Polypeptide in Aqueous Urea: Dipole Orientation or Hydrogen Bonding?

A delicate balance between preferential interaction, hydrogen bonding and dipole-dipole interactions determines polyalanine α-helix (un)folding in aqueous urea. This study clarifies and reconciles existing literature and highlights an operational understanding of polypeptide interactions in binary solutions, which is critical for designing biocompatible materials.

A delicate balance between preferential interaction, hydrogen bonding and dipole-dipole interactions determines polyalanine alpha-helix (un)folding in aqueous urea. This study clarifies and reconciles existing literature and highlights an operational understanding of polypeptide interactions in binary solutions, which is critical for designing biocompatible materials.

Detail of a simulation snapshot showing a polyalanine alpha-helix (purple ribbon) and some neighbouring urea molecules (red: O, blue: N, grey: C and white spheres: H). Water molecules are not included for clarity. This image illustrates the competing interactions driving alpha-helix (un)folding in aqueous urea. After dehydrating the first solvation shell due to long-range dispersion forces, antiparallel urea-residue dipole-dipole (represented by orange and green arrows, respectively) interactions help stabilise the alpha-helix. Urea molecules sitting at the alpha-helix align with dipole moments in a head-to-tail configuration, favouring the formation of urea--residue hydrogen bonds (represented by solid yellow lines) that ultimately contribute to unfolding.