Both circular dichroism (CD) and MMS are spectroscopic techniques that measure protein secondary structures. Both these techniques are known for their high sensitivities and the ability to provide accurate assessment of the secondary structures. These techniques differ by their principles. Because proteins are chiral molecules, they interact with circularly polarized light, and the different secondary structures in protein give rise to differential absorbance upon interactions with left-handed and right-handed polarized light. CD uses this principle to detect the different secondary structures in proteins. MMS on the other hand, probes the vibrationa lresponses of the backbone carbonyl groups of the protein. For CD, the signal quality depends on the total absorbance of a sample. Because of this limitation, the concentration range for CD is narrow (0.01-1 mg/mL) and the buffer compatibility is poor. In contrast, because MMS uses IR spectroscopy andallows for real-time buffer subtraction, it allows a wide range of absorbance and is not limited by buffer signals. MMS can measure samples at a wide concentration range (0.1-200 mg/mL) and is compatible with most buffers and excipients. A direct comparison between CD, FTIR and MMS is given in this application note:
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MMS Measures Protein Misfolding and Protein Aggregation