Numerous examples could be shown where electrostatic interactions are of key importance. Among them are protein folding and protein–protein interactions, which are often governed by a delicate balance of hydrophobic and ionic interactions, protein aggregation, and protein–ligand binding. The contribution of protein surface ion pairs to their stability is also widely observed. Rational design of surface charge–charge interactions led to the increased stability of proteins.Electrostatic interactions are also involved in recognition processes in protein–nucleic acid systems, formation of cooperative salt bridges and electrostatic zippers, and many other macromolecular systems containing charged residues.