A combination of simulation and experiment is used to demonstratethat the sensitivity of a family of3D/4D NMR experiments used to assign resonances and to obtainstructural restraints in proteins is improved bypartial random deuteration; the improvement increases as thecorrelation time of the protein becomes longer. Theresults suggest that deuteration at a level of ∼50% optimizes thesensitivity of experiments which are used to assignsidechain 1H and 13C resonances by correlatingthem with the resonances from backbone nuclei. In addition,thislevel of deuteration is also a good compromise for recording NOESYexperiments. Using this approach, it shouldbe possible to determine structures of larger proteins.
