A combination of simulation and experiment is used to demonstrate that the sensitivity of a family of 3D/4D NMR experiments used to assign resonances and to obtain structural restraints in proteins is improved by partial random deuteration; the improvement increases as the correlation time of the protein becomes longer. The results suggest that deuteration at a level of similar to 50% optimizes the sensitivity of experiments which are used to assign sidechain H-1 and C-13 resonances by correlating them with the resonances from backbone nuclei. In addition, this level of deuteration is also a good compromise for recording NOESY experiments. Using this approach, it should be possible to determine structures of larger proteins.