Comparison of ring current methods for use in molecular modeling refinement of NMR derived three-dimensional...

A comparison between three different methods commonly used to estimate ring current effects on chemical shifts is presented. Haigh-Mallion, Johnson-Bovey, and classical point-dipole approximations were used to estimate the ring current contribution to chemical shifts for protons in several proteins for which both detailed X-ray crystal structures and chemical shift assignments were available. For the classical point-dipole model, new proportionality constants were calculated by fitting to ring current estimations from both the quantum-mechanical Haigh-Mallion and semiclassical Johnson-Bovey methods and compared with the previously used point-dipole constant of Perkins and Dwek. Statistical analysis of the predictions obtained by all methods indicates that the point-dipole approximation parametrized against quantum-mechanical data is superior to the previously used classical model, comparable to Johnson-Bovey calculations, and slightly poorer than predictions from the Haigh-Mallion theory. The implementation of a pseudoenergy penalty term for use in structure refinement from chemical shift data based on the classical point-dipole model is described, and its usefulness in cases where other NMR information is limited is discussed with a specific example.