Understanding protein structure: using scop for fold interpretation.

The structure of a protein can elucidate its function, in both general and specific terms, and its evolutionary history. Extracting this information, however, requires a knowledge of the structure and its relationships with other proteins. These two aspects are not independent, for an understanding of the structure of a single protein requires a general knowledge of the folds that proteins adopt, while an understanding of relationships requires detailed information about the structures of many proteins. Fortunately, this complex problem with its intertwined requirements is not insurmountable, for two reasons. First, protein structures can be fundamentally understood in ways that most of their sequences cannot. The comprehensibility of protein structures derives from the relatively few secondary structure elements in a given domain and the fact that the arrangement of these elements is greatly restricted by physics and probably by evolution. Second, resources are now available to aid recognition of the relationships between protein structures. The structural classification of proteins (scop) database hierarchically organizes proteins according to their structures and evolutionary origin. 1 As such, it forms a resource that allows researchers to learn about the nature of protein folds, to focus their investi-