Benchmarking the Water-Peptide Interaction

Abstract

The interaction between water molecules and the hydration sites of peptides is critical for any quantitative modeling of solvated peptides. We address this interaction for the successive hydration of two peptides for which accurate experimental reference data exist:Ac-Ala5-LysH+ (non-helical) and Ac-Ala8-LysH+ (helical). In particular, finite-temperature Gibbs reference water binding energies ΔG0 and equilibrium constants are known [1,2]. In contrast, earlier force-field predicted preferred water binding sites do not agree with one another. We present an exhaustive first-principles study (density-functional theory based on the van der Waals corrected PBE functional) that demonstrates: (i) There is a close competition between possible hydration sites (protonated carboxyl group or ammonium group). The preferred first hydration site breaks an intramolecular bond of the ammonium group in the unsolvated molecule. (ii) Calculated ΔG0(T) are in remarkable agreement with experimental data. Lowest-energy H2O H-bond networks are predicted for up to five H2O molecules, and the connection to the solvated state is explored by ab initio molecular dynamics with up to 152 H2O molecules.[1] Int. J. Mass Spec. 236, 81 (2004)[2] J. Am. Chem. Soc. 126, 8454 (2004).