Abstract: | To elucidate, at a molecular level, how cosolvents influence protein stability, it is indispensable to understand the distribution of water and cosolvent molecules around proteins. Calculation of excess solvation numbers of water and cosolvents serves this purpose, and I show that they can be extracted from preferential interaction parameter and volumeric data via the Kirkwood-Buff theory. This scheme was applied to trehalose and glycerol (stabilizers) and urea (denaturant). Important insights from the application include stabilizer-induced enhancement of protein hydration, which, together with the stabilizer's exclusion from protein surfaces, may contribute to protein stabilization at high osmolyte concentrations. |