Water Adsorption at Two Unsolvated Peptides with a Protonated Lysine Residue: From Self-Solvation to Solvation

We study the initial steps of the interaction of water molecules with two unsolvated peptides: Ac-Ala5-LysH+ and Ac-Ala8-LysH+. Each peptide has two primary candidate sites for water adsorption near the C-terminus: a protonated carboxyl group and the protonated ammonium group of LysH+, which is fully hydrogen-bonded (self-solvated) in the absence of water. Earlier experimental studies have shown that H2O adsorbs readily at Ac-Ala5-LysH+ (a non-helical peptide) but with a much lower propensity at Ac-Ala8-LysH+ (a helix) under the same conditions. The helical conformation of Ac-Ala8-LysH+ has been suggested as the origin of the different behavior. We here use first-principles conformational searches (all-electron density functional theory based on a van der Waals corrected version of the PBE functional, PBE+vdW) to study the microsolvation of Ac-Ala5-LysH+ with one to five water molecules and the monohydration of Ac-Ala8-LysH+. In both cases, the most favorable water adsorption sites break intramolecular hydrogen bonds associated with the ammonium group, in contrast to earlier suggestions in the literature. A simple thermodynamic model yields Gibbs free energies ΔG0(T) and equilibrium constants in agreement with experiments. A qualitative change of the first adsorption site does not occur. For few water molecules, we do not consider carboxyl deprotonation or finite-temperature dynamics, but in a liquid solvent, both effects would be important. Exploratory ab initio molecular dynamics simulations illustrate the short-time effects of a droplet of 152 water molecules on the initial unsolvated conformation, including the deprotonation of the carboxyl group. The self-solvation of the ammonium group by intramolecular hydrogen bonds is lifted in favor of a solvation by water.