Protein redesign

It has been demonstrated that, for a number of proteins, it is possible to dramatically alter the connectivities between elements of secondary structure. Remarkably large loop insertions are tolerated and many redesigns have generated proteins that successfully fold to stable, active structures. Some redesigns have been entirely the choice of the investigators, whereas others have incorporated a randomization and selection step to identify optimal sequences. These studies have provided basic guidelines for the rational manipulation of protein structure and stability, they have allowed the dissection of folding pathways and they have generated proteins with the potential for practical therapeutic applications.