Intramolecular interactions at protein surfaces and their impact on protein function

Protein surfaces play a key role in the biological function of proteins. Consequently, structural features of protein surfaces are the basis for predicting function from structure. A well-established principle of binding by proteins is that ligands must compete with water and other small molecules to form interactions with protein surfaces. A less obvious issue, and the emphasis of this article, is that ligands must also compete with interactions among residues at protein surfaces. Results from structural surveys, a variety of experimental studies and computations suggest that intramolecular interactions are present at protein surfaces and that the energetics of these interactions can change when proteins bind to other molecules.