Core physical principles of allostery

Allostery is a basic property of proteins that represents the functional coupling of distantly positioned amino acids. In different manifestations, this property underlies signal transmission, cooperative binding, regulation, catalysis, and evolvability-the elementary features of molecular processes in living cells. While thermodynamic models have provided excellent abstract phenomenological descriptions and classifications of allostery, comparable descriptions and classifications at a more microscopic level, where the nature of physical interactions is specified, are lacking. Starting from minimal assumptions, we derive the essential physical principles of allostery and show that previously described forms of allostery can be viewed as specific implementations of a combination of two core principles: actuation of a soft mode and switching between two states. Organizing allostery by these principles may provide a simpler and more universal language to describe the physics of allostery in proteins.