An electrostatic interaction between amino acid sidechains in proteins.

When a positively charged amine encounters a negatively charged carboxyl group, they may form a charge pair called a salt bridge. The name comes from the fact that the ionic attraction between the two groups forms a neutral salt which bridges two amino acids, forming a stable connection in the protein.

    ... C - O- +H3N ...

When a charge group is buried inside of a protein, the energetic penalty of desolvating the charge must be somehow made up for during the folding process. A salt bridge is one of the few ways a charged residue can stably remain buried inside of a protein. The effect of salt bridges on protein stability can be directly studied by altering the pH of the solution. Since both amines and carboxyls have pKas that are titratable within reasonable ranges, one can disrupt a salt bridge by neutralizing the charge on either partner. The pKa of both the carboxyl and the amine change in the salt bridge as opposed to their values free in solution. There is a direct thermodynamic linkage between the stability of the salt bridge and the change in pKa for both groups.

Salt bridges are believed to contribute to the stability of proteins from thermophillic organisms. This has yet to be conclusively shown. Directed evolution studies, where mesophilic (normal temperature) proteins are encouraged to be stable at higher temperatures, often evolve salt bridges on the surface of the protein.

For other protein stabilization forces, see: