Microhydration of Protonated Nα-Acetylhistidine: A Theoretical Approach

Area of Science:

• Computational Chemistry
• Molecular Dynamics
• Biophysics

Background:

• Protonated amino acids play crucial roles in biological systems.
• Understanding hydration effects on amino acid protonation is vital for biochemical studies.
• Nα-acetylhistidine is a model compound for studying histidine protonation.

Purpose of the Study:

• To explore potential energy surfaces of protonated Nα-acetylhistidine with 0-3 water molecules.
• To investigate the combined efficacy of hierarchical and genealogical computational approaches.
• To accurately calculate hydration enthalpies using high-level theoretical methods.

Main Methods:

• Utilized a hybrid hierarchical and genealogical (Darwin family tree) approach.
• Employed the polarizable AMOEBA force field and M06 functional for conformational searching.
• Calculated hydration enthalpies using high-level theoretical methods, including G4MP2 and MP2.
• Validated computational methods against experimental data for model cations.

Main Results:

• The combined computational approach recovered a greater number of conformers than individual methods.
• Calculated hydration enthalpies showed excellent agreement with experimental data for model compounds.
• The first hydration enthalpy of protonated Nα-acetylhistidine was found to be approximately 10 kJ mol⁻¹ lower than that of imidazolium.

Conclusions:

• The hybrid computational strategy is effective for exploring complex potential energy surfaces.
• The study provides accurate hydration enthalpy values for protonated Nα-acetylhistidine.
• The local environment significantly influences the hydration enthalpy of the charged moiety.