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

We report on new X-ray solution scattering experiments and molecular dynami cs simulations conducted for increasing solute concentrations of N-acetyl-a mino acid-amides and -methylamides in water, for the amino acids leucine, g lutamine, and glycine. As the concentration increases, the main diffraction peak of pure water at Q = 2.0 Angstrom(-1) shifts to smaller angle for the larger leucine and glutamine amino acids, and a new diffraction peak grows in at Q similar to 0.8 Angstrom(-1) for only the hydrophobic amino acid le ucine. The unaltered value of the peak position at Q similar to 0.8 Angstro m(-1) over a large concentration range suggests that a stable and ordered l eucine solute-solute distribution is sustained. Simulations of the distribu tions 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 hydropho bic solutes into one large cluster. The scattering results for the hydropho bic leucine amino acid are contrasted with experiments and simulations of t he model hydrophilic side chain glutamine and the model backbone glycine. T he self-assembly process of protein folding modeled with these experiments, in particular the condensation to a hydrophobic core, shares similar issue s with the desolvation phenomena that are important in drug discovery.