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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.