Electrostatic effects dominate many aspects of protein behavior. When polypeptide chains fold up, most polar side chains seek the exterior, where they can be solvated. Water bound in the interior has been found between the domains of enzymes of the chymotrypsin family, and between the subunits of hemoglobin and tobacco mosaic virus protein. Assembly of this protein from disk to virus is triggered by electrostatic interactions between neighboring subunits. Lysozyme stabilizes the constellation of charges involved in the transition state of its substrate by both permanent and induced dipoles. All factors that lower the oxygen affinity of hemoglobin act by strengthening the salt bridges that constrain its quaternary deoxy (T) structure. Enzymes of thermophile bacteria owe their extra stability mostly to additional salt bridges. The rate of denaturation of hemoglobins by alkali is determined by the ionization of internal side chains with pK's of about 12.