PNNL

Abstract

The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Activity coefficients of urea solutions are calculated to explore the mechanism of its solution properties, which form the basis for its well-known use as a strong protein denaturant. We perform free energy simulations of urea solutions in different urea concentrations using two urea models (OPLS and KBFF models) to calculate and decompose the activity coefficients. For the case of urea, we clarify the concept of the ideal solution in different concentration scales and standard states and its effect on our subsequent analysis. The analytical form of activity coefficients depends on the concentration units and standard states. For both models studied, urea displays a weak concentration dependence for excess chemical potential. However, for the OPLS force-field model, this results from contributions that are independent of concentration to the van der Waals and electrostatic components whereas for the KBFF model those components are nontrivial but oppose each other. The strong ideality of urea solutions in some concentration scales (incidentally implying a lack of water perturbation) is discussed in terms of recent data and ideas on the mechanism of urea denaturation of proteins.