COMPARISON OF RING CURRENT METHODS FOR USE IN MOLECULAR MODELING REFINEMENT OF NMR DERIVED 3-DIMENSIONAL STRUCTURES

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 a nd 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-Ma llion and semiclassical Johnson-Bovey methods and compared with the pr eviously used point-dipole constant of Perkins and Dwek. Statistical a nalysis of the predictions obtained by all methods indicates that the point-dipole approximation parametrized against quantum-mechanical dat a is superior to the previously used classical model, comparable to Jo hnson-Bovey calculations, and slightly poorer than predictions from th e Haigh-Mallion theory. The implementation of a pseudoenergy penalty t erm for use in structure refinement from chemical shift data based on the classical point-dipole model is described, and its usefulness in c ases where other NMR information is limited is discussed with a specif ic example.