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.
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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.