  Urea denatures proteins due to its strong tendency to dehydrate the first
solvation shell via urea-residue preferential binding. However, even after
extensive experimental and computational investigations, the influence of urea
on the stability of secondary structures remains elusive. For example, contrary
to the common understanding, experimental studies have indicated that specific
polypeptides, such as poly-alanine or alanine-rich systems, may even show an
improved tendency to form secondary structures in aqueous urea. We investigate
this seemingly counter-intuitive behaviour using over 15$\mu$s long all-atom
simulations. These results show how a delicate balance between the localized
dipole orientations and hydrogen bonding dictates polypeptide solvation in
aqueous urea. Our work establishes a structure-property relationship that
highlights the importance of microscopic dipole-dipole
orientations/interactions for the operational understanding of macroscopic
protein solvation.
