Molecular Thermodynamics of Protein Systems

The overall aim of this chapter is to provide an introduction to thermodynamics of protein solutions applied to understanding how cosolvents, such as salts, osmolytes, or denaturants, impact upon protein stability and denaturation and protein phase behavior. This is especially relevant for any type of protein formulation or in bioseparation processes where a key variable is the cosolvent composition, which often needs to be manipulated to maintain protein stability and/or control protein solubility. The emphasis is on a molecular perspective, which is achieved by relating thermodynamic properties to protein–solvent and protein–protein interactions. Using a molecular approach provides a link through knowledge of intermolecular interactions between protein solution behavior and the protein physicochemical properties and solvent conditions, which, in turn, allows for some level of predictability.