Solution X-ray scattering as a probe of hydration-dependent structuring of aqueous solutions

Abstract

We report on new X-ray solution scattering experiments and molecular dynamics simulations conducted for increasing solute concentrations of N-acetyl-amino acid-amides and -methylamides in water, for the amino acids leucine, glutamine, and glycine. As the concentration increases, the main diffraction peak of pure water at Q = 2.0 Å^-1 shifts to smaller angle for the larger leucine and glutamine amino acids, and a new diffraction peak grows in at Q ∼ 0.8 Å^-1 for only the hydrophobic amino acid leucine. The unaltered value of the peak position at Q ∼ 0.8 Å^-1 over a large concentration range suggests that a stable and ordered leucine solute–solute distribution is sustained. Simulations of the distributions of leucines in water that reproduce the experimental observable show that mono-dispersed to small molecular aggregates of two to six hydrophobic amino acids are formed, as opposed to complete segregation of the hydrophobic solutes into one large cluster. The scattering results for the hydrophobic leucine amino acid are contrasted with experiments and simulations of the model hydrophilic side chain glutamine and the model backbone glycine. The self-assembly process of protein folding modeled with these experiments, in particular the condensation to a hydrophobic core, shares similar issues with the desolvation phenomena that are important in drug discovery.