Hydration - Competition with Peptide Self-Solvation

    The charge site on a peptide is stabilized by solvation, which can be accomplished either by other portions of the peptide itself or by external solvents such as water. The competition with self-solvation can, therefore, have an effect on hydration. Temperature-dependent equilibrium experiments and molecular modeling reveal that peptides with a greater degree of self-solvation have lower water binding energies.

Molecular mechanics structures and experimental water binding energies for
(Ac-AAAAK + H)⁺·(H₂O) and (Ac-AAKAA + H)⁺·(H₂O). These two acetylated (Ac) pentapeptides differ only in the position of the lysine residue (K), yet have different experimental water binding energies. When lysine is at the N-terminus (structure on left), water is bound 1.6 kcal/mol more weakly than when lysine is in the center position (structure on right). Molecular mechanics studies show that this is due to competition with peptide self-solvation. Lysine is the charge-carrying group for both peptides, but when it is at the end of the peptide, it is able to form three hydrogen bonds with the rest of the peptide. When lysine is in the middle position, it can only form two intramolecular hydrogen bonds. However, it can form a third hydrogen bond with water. Because the water molecule in (Ac-AAKAA + H)⁺·(H₂O) is bound directly to the -NH₃⁺ group on lysine it forms a stronger bond than it does in (Ac-AAAAK + H)⁺·(H₂O).