Allostery in protein domains reflects a balance of steric and hydrophobic effects.

Allosteric conformational change underlies biological function in many proteins. Allostery refers to a conformational event in which one region of a protein undergoes structural rearrangement in response to a stimulus applied to a different region of the same protein. Here, I show for a variety of proteins that a simple, phenomenological model of the dependence of protein conformation on hydrophobic burial energy allows one to compute low-energy conformational fluctuations for a given sequence by using linear programming to find optimized combinations of sequence-specific hydrophobic burial modes that satisfy steric constraints. From these fluctuations one may calculate allosteric couplings between different sites in a protein domain. Although the physical basis of protein structure is complex and multifactorial, a simplified description of conformational energy in terms of the hydrophobic effect alone is sufficient to give a mechanistic explanation for many biologically important allosteric events.