Efficient acquisition of high-resolution 4-D diagonal-suppressed methyl-methyl NOESY for large proteins

► Diagonal suppression reduces the dynamic range of signals in the 4-D CH3-CH3 NOESY experiment. ► Diagonal suppression reduces aliasing artifacts left over by CLEAN for ultrasparse sampling. ► Diagonal suppression enables detection of the majority of NOEs for methyl groups within 5 Å of MBP. ► Diagonal suppression enables detection of NOE crosspeaks for methyl groups over 7 Å apart in MBP.