TIME-AVERAGED AND ENSEMBLE-AVERAGED DIRECT NOE RESTRAINTS

NMR data are collected as time- and ensemble-averaged quantities. Yet, in commonly used methods for structure determination of biomolecules, structures are required to satisfy simultaneously a large number of c onstraints. Recently, however, methods have been developed that allow a better fit of the experimental data by the use of time- or ensemble- averaged restraints. Thus far, these methods have been applied to stru cture refinement using distance and J-coupling restraints. In this pap er, time and ensemble averaging is extended to the direct refinement w ith experimental NOE data. The implementation of time- and ensemble-av eraged NOE restraints in DINOSAUR is described and illustrated with ex perimental NMR data for crambin, a 46-residue protein. Structure refin ement with both time- and ensemble-averaged NOE restraints results in lower R-factors, indicating a better fit of the experimental NOE data.