 In protein work, NOEs are used to create constraints on intramolecular distances.In this method, each proton pair is considered in isolation and NOESY cross peak intensities are compared with a reference cross peak from a proton pair of fixed distance, such as a geminal methylene proton pair or aromatic ring protons.This simple approach is reasonably insensitive to the effects of spin diffusion or non-uniform correlation times and can usually lead to definition of the global fold of the protein, provided a sufficiently large number of NOEs have been identified.