The relation between intrinsic protein conformational changes and ligand binding

1Structural changes in proteins allow them to exist in several conformations. Non-covalent interactions with ligands drive the structural changes, thereby allowing the protein to perform its biological function. Recent findings suggest that many proteins are always in an equilibrium of different conformations and that each of these conformations can be formed by both the ligand-free and ligand-bound protein. By using classical statistical mechanics, we derived the equilibrium probabilities of forming a conformation with and without ligand. We found, under certain conditions, that increasing the probability of forming a conformation by the ligand-free protein also increases the probability of forming the same conformation when the protein has a ligand bound. Further, we found that changes in the conformational equilibrium of the ligand-free protein can increase or decrease the affinity for the ligand.