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Abstract:
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 Cterminus:
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 di!erent behavior. We
here use "rst-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 "ve 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 "rst adsorption site does not
occur. For few water molecules, we do not consider carboxyl deprotonation or "nite-temperature dynamics, but in a liquid
solvent, both e!ects would be important. Exploratory ab initio molecular dynamics simulations illustrate the short-time e!ects 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.
