POSSIBLE FOLDING PATHWAY OF BOVINE PANCREATIC RNASE

A theoretical pathway for the folding of RNase into its native conformation is derived from the contact map computed from crystallographic coordinates. The pathway is based on the hypothesis of Tanaka and Scheraga, according to which localized conformations stabilized by short- and medium-range interactions form before those conformational features that are stabilized primarily by long-range interactions. The pathway deduced from the contact map agrees with experimental information on intermediates detected in thermal unfolding of RNase and in immunochemical studies on the formation of stable antigenic sites when reduced RNase is oxidized with glutathione. Ambiguites in the interpretation of the contact map are resolved by the combination of structural information contained in the contact map and experimental information.