Protein Association in Solution: Statistical Mechanical Modeling

Protein molecules associate in solution, often in clusters beyond pairwise, leading to liquid phase separations and high viscosities. It is often impractical to study these multi-protein systems by atomistic computer simulations, particularly in multi-component solvents. Instead, their forces and states can be studied by liquid state statistical mechanics. However, past such approaches, such as the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, were limited to modeling proteins as spheres, and contained no microscopic structure–property relations. Recently, this limitation has been partly overcome by bringing the powerful Wertheim theory of associating molecules to bear on protein association equilibria. Here, we review these developments.