CHEMICAL-SHIFTS AND 3-DIMENSIONAL PROTEIN STRUCTURES

During the past three years it has become possible to compute ab initi o the C-13, N-15 and F-19 NMR chemical shifts of many sites in native proteins. Chemical shifts are beginning to become a useful supplement to more established methods of solution structure determination, and m ay find utility in solid-state analysis as well. From C-13 NMR, inform ation on phi, psi and chi torsions can be obtained, permitting both as signment verification, and structure refinement and prediction. For N- 15, both torsional and hydrogen-bonding effects are important, while f or F-19, chemical shifts are primarily indicators of the local charge field. Chemical shift calculations are still slow, but shielding hyper surfaces - the shift as a function of the dihedral angles that define the molecular conformation - are becoming accessible. Over the next fe w years, theoretical and computer hardware improvements will enable mo re routine use of chemical shifts in structural studies, including the study of metal-ligand interactions, the analysis of drug and substrat e binding and catalysis, the study of folding/unfolding pathways, as w ell as the characterization of conformational substates. Rather than s imply being a necessary prerequisite for multidimensional NMR, chemica l shifts and chemical shift non-equivalence due to folding are now beg inning to be useful for structural characterization.