Protonated arginine and protonated lysine: hydration and its effect on the stability of salt-bridge structures

Using a mass spectrometer equipped with a drift cell, water binding energies of protonated arginine (ArgH+) and protonated lysine (LysH+) were determined in equilibrium experiments and supplementary calculations at the B3LYP/6-311++G** level of theory. The binding energy of the first water molecule was measured to be 10.3 and 10.9 kcal/mol for ArgH+ and LysH+, respectively. Water binding energies decrease with increasing degree of hydration reaching values of 6-7 kcal/mol for the fourth and fifth water molecule. Theory reproduces this trend of decreasing binding energies correctly and theoretical water binding energies agree with experiment quantitatively within 2 kcal/mol. Lowest-energy theoretical structures of ArgH+ and LysH+ are characterized by protonated side chains and neutral alpha-amino and carboxyl groups which form intramolecular hydrogen bonds to the ionic group (charge solvation or CS structures). The salt bridge (SB) structures with two cationic groups (side chain and alpha-amine) and one anionic group (carboxyl) are 13.1 and 9.3 kcal/mol higher in energy for ArgH+ and LysH+, respectively. Theory indicated that the first water molecule binds to the ionic group of the CS structures of ArgH+ and LysH+. With increasing degree of hydration intramolecular interactions are replaced one by one with water bridges with water inserted into the intramolecular hydrogen bonds. Whereas the global minima of ArgH+.(H2O)n and LysH+.(H2O)n, n<7, were calculated to represent CS structures, 7-fold hydrated CS and SB structures, ArgH+.(H2O)7 and LysH+.(H2O)7, are nearly isoenergetic (within <1 kcal/mol).