On the binding affinity of macromolecular interactions: daring to ask why proteins interact
The typical environment for biomolecules in vivo is highly crowded. Under such conditions chemical activities, rather than simply concentrations, govern the behavior of the molecules. In this chapter we discuss the underlying solvation principles that give rise to the chemical activities. We focus on simple experimentally accessible examples, macromolecular crowding, protein folding, and ligand binding under crowded conditions. We discuss effects of high concentrations of both macromolecules and small molecules in terms of the Kirkwood-Buff theory, which couples solution structure to thermodynamics.