To facilitate the process of proteindesign and learn the basic rules that control the structure and stability of proteins, combinatorial methods have been developed to select or screen proteins with desired properties from libraries of mutants. One such method uses phage-display and proteo-lysis to select stably folded proteins. This method does not rely on specific properties of proteins for selection. There-fore, in principle it can be applied to any protein. Since its first demonstration in 1998, the method has been used to create hyperthermophilic proteins, to evolve novel folded domains froma librarygeneratedby combinatorial shuffling of polypeptide segments and to convert a partially unfolded structure to a fully folded protein
