PROTEIN PHI-DIHEDRAL AND PSI-DIHEDRAL RESTRAINTS DETERMINED FROM MULTIDIMENSIONAL HYPERSURFACE CORRELATIONS OF BACKBONE CHEMICAL-SHIFTS ANDTHEIR USE IN THE DETERMINATION OF PROTEIN TERTIARY STRUCTURES

The chemical shifts of the backbone atoms of proteins can be used to o btain restraints that can be incorporated into structure determination methods. Each chemical shift can be used to define a restraint and th ese restraints call be simultaneously used to define the local, second ary structure features. The global fold call be determined by a combin ed use of the chemical shift based restraints along with the long-rang e information present in the NOEs of partially deuterated proteins or the amide-amide NOEs but not from such limited NOE data sets alone. Th is approach has been demonstrated to be capable of determining the ove rall folding pattern of four proteins. This suggests that solution-sta te NMR methods can be extended to the structure determination of large r proteins by using the information present in the chemical shifts of the backbone atoms along with the data that call be obtained on a smal l number of labeled forms.