Assessing accumulated solvent near a macromolecular solute by preferential interaction coefficients

Area of Science:

• Biophysical Chemistry
• Computational Chemistry
• Solution Chemistry

Background:

• Biological macromolecules are frequently studied in mixed solvent systems.
• Understanding solvent interactions with macromolecules is crucial for various biological and chemical applications.
• The preferential interaction coefficient (Gamma(3)) is a key parameter for characterizing solvent composition near macromolecules.

Purpose of the Study:

• To clarify the definition and measurement of the preferential interaction coefficient (Gamma(3)) in mixed solvents.
• To investigate the composition of the 'local domain' surrounding a macromolecule.
• To explore the relationship between Gamma(3) and the surface solvent distribution (rho(x)) using a simplified model.

Main Methods:

• Performed computer simulations on a two-dimensional (2D) model system.
• The model consisted of a hard-wall solute representing a macromolecule in a mixed solvent of hard disks.
• Simultaneously calculated the preferential interaction coefficient (Gamma(3)) and the radial solvent distribution function (rho(x)).

Main Results:

• The boundary of the local domain is effectively defined by the outer limit of the first cosolvent layer.
• The preferential interaction coefficient (Gamma(3)) primarily reflects solvent molecules in close proximity to the macromolecule.
• Accurate calculation of Gamma(3) requires counting water and cosolvent molecules within the same spatial region.

Conclusions:

• The study provides a clearer operational definition for the local domain and its contribution to Gamma(3).
• The findings suggest that simplified 2D models can offer valuable insights into 3D macromolecule-solvent interactions.
• These results are applicable when cosolvents are not strongly repelled by the macromolecule and long-range solvent structuring is minimal.