Evidence for microscopic, long-range hydration forces for a hydrophobic amino acid

Area of Science:

• Biophysics
• Physical Chemistry
• Computational Chemistry

Background:

• Understanding solute-solute interactions in aqueous solutions is crucial for various biological and chemical processes.
• N-acetyl-leucine-amide (NALA) serves as a model compound for studying amino acid behavior in solution.
• Dilute concentrations pose challenges for characterizing molecular correlations.

Purpose of the Study:

• To isolate and analyze N-acetyl-leucine-amide (NALA) correlations in aqueous solution.
• To determine the pair distribution function of NALA molecules at dilute concentrations.
• To investigate the implications of hydration forces on molecular interactions and biological processes.

Main Methods:

• Combined neutron solution scattering experiments with molecular dynamics simulations.
• Isolated an excess experimental signal attributed solely to NALA-NALA correlations.
• Tested different pair distribution functions (gas, cluster, aqueous) against experimental data.

Main Results:

• Successfully isolated NALA-NALA correlations in dilute aqueous solutions.
• Ruled out gas and cluster pair distribution functions for NALA.
• The aqueous pair distribution function, showing a solvent-separated minimum, best reproduced the experimental data.
• Indicated the presence of longer-ranged correlations in the aqueous form.

Conclusions:

• Small-angle scattering data can reveal solute-solute correlations, length scales, and thermodynamic consequences even at dilute concentrations.
• Hydration forces at the microscopic level, as suggested by the data, significantly influence protein folding and ligand binding.
• The study provides a robust method for analyzing molecular interactions in solution.