Journal of Biomolecular NMR

, Volume 56, Issue 4, pp 331-335

Divide and conquer is always best: sensitivity of methyl correlation experiments

  • Kaustubh SinhaAffiliated withDepartment of Biological Sciences, Carnegie Mellon University
  • , Linda Jen-JacobsonAffiliated withDepartment of Biological Sciences, University of Pittsburgh
  • , Gordon S. RuleAffiliated withDepartment of Biological Sciences, Carnegie Mellon University Email author 

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The HMCM [CG]CBCA experiment (Tugarinov and Kay in J Am Chem Soc 125:13868–13878, 2003) correlates methyl carbon and proton shifts to Cγ, Cβ, and Cα resonances for the purpose of resonance assignments. The relative sensitivity of the HMCM[CG]CBCA sequence experiment is compared to a divide-and-conquer approach to assess whether it is best to collect all of the methyl correlations at once, or to perform separate experiments for each correlation. A straightforward analysis shows that the divide-and-conquer approach is intrinsically more sensitive, and should always be used to obtain methyl-Cγ, Cβ, and Cα correlations. The improvement in signal-to-noise associated with separate experiments is illustrated by the detection of methyl-aliphatic correlations in a 65 kDa protein-DNA complex.


Methyl resonance assignment Protein-DNA complex Pulse sequence