CHAPTER 5.1: Stabilization of Peptides and Proteins by Engineered Disulfide Bonds

It is often desirable to increase the stability of proteins. A method for protein stabilization that has been successful in a wide range of applications is disulfide engineering. This method entails the creation of novel disulfide bonds in proteins of interest. An effective approach towards accomplishing this goal is to analyze a structural model of the target protein to identify a residue pair that is oriented in a manner consistent with disulfide formation, then mutate the residues to cysteines. This chapter reviews computational methods that have been developed to assist in disulfide engineering. In addition, a range of successful disulfide engineering applications, from stabilization of industrial enzymes to improvements in vaccine stability and efficacy, are discussed.