An optimized NMR experiment that combines the advantages of methyl-TROSY and SOFAST-HMQC has been developed. It allows the recording of high quality methyl. H-1-C-13 correlation spectra of protein assemblies of several hundreds of kDa in a few seconds. The SOFAST-methyl-TROSY-based experiment offers completely new opportunities for the study of structural and dynamic changes occurring in molecular nanomachines while they perform their biological function in vitro.