The measurement of C-13 directed-detected paramagnetic relaxation enhancements (PREs) on spin-labeled proteins combines the efficacy of PREs for the detection of long-range distance information with the favorable sensitivity and resolution of C-13 direct-detected experiments. The C-13 PREs provide long-range distance restraints to map binding interfaces in proteins and protein complexes and are especially useful for studies of high-molecular weight perdeuterated molecules.