Comparison of Ring Current Methods for Use in Molecular Modeling Refinement of NMR Derived Three-Dimensional Structures

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Abstract
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.