The salt bridge formation and stability in the terminated lysine-glutamate dipeptide is investigated
in water clusters of increasing size up to the limit of bulk water. Proton transfer dynamics between
the acidic and basic side chains is described by DFT-based Born-Oppenheimer molecular dynamics
simulations. While the desolvated peptide prefers to be in its neutral state, already the addition
of a single water molecule can trigger proton transfer from the glutamate side chain to the
lysine side chain, leading to a zwitterionic salt bridge state. Upon adding more water molecules we
find that stabilization of the zwitterionic state critically depends on the number of hydrogen bonds
between side chain termini, the water molecules, and the peptidic backbone. Employing classical
molecular dynamics simulations for larger clusters, we observed that the salt bridge is weakened
upon additional hydration. Consequently, long-lived solvent shared ion pairs are observed for about
30 water molecules while solvent separated ion pairs are found when at least 40 or more water
molecules hydrate the dipeptide. These results have implications for the formation and stability of salt
bridges at partially dehydrated surfaces of aqueous proteins.