Fluctuations and averaging of proton chemical shifts in the bovine pancreatic trypsin inhibitor.

The effects of motional averaging on the aromatic ring-current contribution to the proton chemical shifts in proteins are examined. Atomic trajectories obtained from a 96-ps molecular dynamics simulation of the bovine pancreatic trypsin inhibitor are used in conjunction with the Johnson-Bovey model of ring-current shifts to calculate the time evolution of the proton chemical shifts. Although large high-frequency fluctuations are observed (often greater than +/- 1 ppm), the average shift values in most cases are close to those obtained from the average structure; for some protons, significant differences are found. The calculated trends are used to probe the relationship between the average structure, atomic motions, and observed values of the proton chemical shifts. It is concluded that chemical shift values are in general most sensitive to the average structure of the protein and, because of the averaging involved, cannot be used directly to probe the short time structural fluctuations.