The application of Kirkwood-Buff theory to study hydration properties of $α$-amino acids

Protein conformational stability and function depend on non-covalent interactions that are strongly influenced by the surrounding environment. To explore protein properties, amino acids are often utilized as model systems. In this study, we determined the densities of seven $α$-amino acids in aqueous solutions between 278.15 K and 308.15 K and calculated the apparent molar volumes. Linear extrapolation yielded standard molar volumes, which were analyzed to characterize amino-acid hydration. The contributions of side chains to the standard molar volume were determined relative to glycine. The standard molar volume increased with temperature, indicating reduced electrostriction of water around the amino acids, consistent with lower hydration numbers at higher temperatures. We employed the Ornstein-Zernike integral equation with hypernetted-chain closure and a coarse-grained Lennard-Jones bead model to calculate pair correlation functions and Kirkwood-Buff integrals, from which standard molar volumes were obtained. The model reproduced the experimental standard molar volumes very well.

💡 Research Summary

This study investigates the hydration properties of seven α‑amino acids (arginine, aspartic acid, glutamic acid, glycine, lysine, serine, and tryptophan) by combining precise experimental density measurements with a statistical‑mechanical analysis based on Kirkwood‑Buff (KB) theory. Densities of aqueous solutions were measured over a temperature range of 278.15 K to 308.15 K at several concentrations, allowing the calculation of apparent molar volumes. Linear extrapolation to infinite dilution yielded standard molar volumes (V°_φ) and the slope S_v, which reflects solute‑solute interactions. The standard molar volumes increase linearly with temperature, indicating a reduction in electrostriction of water around the zwitterionic amino acids and consequently a decrease in hydration numbers at higher temperatures.

To provide a microscopic interpretation, each amino acid and water were modeled as a single isotropic Lennard‑Jones (LJ) bead. Water parameters (σ₁₁ = 0.316 nm, ε₁₁/k_BT = 0.26) reproduce the short‑range structure of the SPC/E model, while amino‑acid bead sizes (σ₂₂) and interaction strengths (ε₂₂/k_BT) were taken from literature. Cross‑interaction parameters were obtained via Lorentz–Berthelot mixing rules. The Ornstein‑Zernike (OZ) integral equation was solved with the hypernetted‑chain (HNC) closure to obtain total (h_ij) and direct (c_ij) correlation functions. In the tracer (infinite‑dilution) limit, pair distribution functions g_ij(r)=1+h_ij(r) were used to compute KB integrals G_ij=4π∫₀^∞