Exploring Cosolvent Effects to Control Biomolecular and Interfacial Interactions

The cosolvent effects on aggregation of biomolecules and adsorption onto solid-liquid interface are studied with MD simulation and a solvation theory. It is first noted that these problems can be addressed in a unified manner by extending the concept of solvation. The energy-representation theory formulated by the presenter is amenable to the extension, and its performance is demonstrated over wide ranges of hydrophobic and hydrophilic solutes. A statistical-mechanical method is then provided to analyze the cosolvent effects on biomolecular interactions. It is seen that the excess chemical potential is stationary against the variation of the distribution function for the configuration of a flexible solute species, and accordingly, the derivative of the excess chemical potential with respect to the cosolvent concentration is determined only by the corresponding derivative of the solvation free energy averaged over the solute configurations. The effect of a cosolvent at low concentrations on a chemical equilibrium can thus be addressed in terms of the difference in the solvation free energy between the pure-water solvent and the mixed solvent with the cosolvent, and all-atom analyses are performed for the aggregation of an 11-residue peptide by employing the energy-representation method to compute the solvation free energy. It is found that when urea or DMSO is added as a cosolvent, the solvation becomes more favorable. The extent of stabilization is smaller for larger aggregate, implying that these cosolvents inhibit the formation of an aggregate. The cosolvent-induced change in the solvation free energy depends on the degree of aggregation more strongly for the urea cosolvent than DMSO. Urea is thus a better inhibitor than DMSO, and it is estimated that the peptide concentration leading to the aggregation increases by orders of magnitude when the cosolvent is added at mol/L scale. The effect of an additive (impurity) on the crystal growth will be analyzed, furthermore. The transfer free energy of the additive to an adsorption site is treated in the framework of the energy-representation theory of solvation, from which a guideline can be formulated for controlling the dependence of the growth rate on the crystal face.