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.