Anisotropic protein-protein interactions due to ion binding

Self-association of proteins is strongly affected by long-range electrostatic interactions caused by equilibrium adsorption of small ions such as protons and multivalent metals. By affecting the molecular net charge, solution pH is thus a widely used parameter to tune stability and phase behavior of proteins. We here review recent studies where the charge distribution is perturbed not only by protons, but also by other binding ions, leading to a rich and inherently anisotropic charge distribution. Focus is on coarse grained simulation techniques, coupled to experiments of protein-protein interaction at varying salt and pH conditions. Finally, and with future bio-colloidal models in mind, we discuss the validity of coarse graining charge anisotropy using electric multipoles.