ABSTRACT
Protein design tests our understanding of how protein sequence relates to structure and function; that is, our progress towards addressing the informational aspect of the proteinfolding problem. In addition, successful protein-design exercises provide tools, concepts, and rules for: (1) engineering existing protein scaffolds (an area that we refer to as protein engineering or protein redesign), and (2) creating altogether new protein structures and functions (de novo protein design). This second endeavor is the ultimate quest for some protein designers, but it is difficult and, by and large, can only be
achieved for a limited number of relatively straightforward protein-folding motifs-for instance, coiled coils and zincfinger peptides-for which good sequence-to-structure relationship are available (1); although, very recently, Baker and colleagues (2) describe the successful computer-aided design of a completely novel globular protein.
