AN APPROACH TO THE STRUCTURE DETERMINATION OF LARGER PROTEINS USING TRIPLE-RESONANCE NMR EXPERIMENTS IN CONJUNCTION WITH RANDOM FRACTIONAL DEUTERATION

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