Enhanced NMR: Proteins yield

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  • Published: Feb 1, 2019
  • Author: David Bradley
  • Channels: NMR Knowledge Base
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Accessible NMR

MIT team and colleagues have developed an enhanced form of protein NMR. Credit: MIT News

A team from Massachusetts Institute of Technology (MIT) has found that they can enhance nuclear magnetic resonance (NMR) spectroscopy in such a way as to facilitate the structure determination of proteins associated with a wide range of diseases.

Robert Griffin and his colleagues suggests that their new approach cuts the time needed to mere minutes whereas previously some protein determinations would have been impossible or at best take many years. Their approach uses short pulses of microwave power. “This technique should open extensive new areas of chemical, biological, materials, and medical science which are presently inaccessible,” explains Griffin.

Sensitivity boost

The sensitivity of conventional NMR depends on polarization. The greater the polarization, the greater sensitivity that is possible. It is usual to exploit stronger and stronger magnetic fields, up to 35 Tesla to increase polarization and extract data from the resulting spectrum. However, Griffin and Richard Temkin of MIT’s Plasma Science and Fusion Center have spent the last quarter of a century developing dynamic nuclear polarization (DNP) to a fine art. In this approach, polarization is essentially transferred from the unpaired electrons of free radicals to the target nuclei, the hydrogen, carbon, nitrogen, or phosphorus.

Standard DNP involve continuous irradiation of the sample with high-frequency microwaves from a gyrotron. This can give NMR spectroscopy a 100-fold. Unfortunately, it is power intense as well as not working well at higher magnetic fields. The MIT team has worked around those problems by using short pulses of microwave radiation instead. They deliver those pulses at a precise frequency and have found that they can enhance polarization by up to 200 times using a fraction of the power (7 percent). This is similar to the improvement achieved with traditional DNP, but it requires only 7 percent of the power. Moreover, the approach works at the higher magnetic fields that offer a clearer view of a molecular structure.

Polarisation transfer

“We can transfer the polarization in a very efficient way, through efficient use of microwave irradiation,” says the team's post-doctoral researcher, Kong Ooi Tan. “With continuous-wave irradiation, you just blast microwave power, and you have no control over phases or pulse length.”

Running a spectrum for a sample that ostensibly might have taken more than a century to complete, the team can carry out a useful analysis in just one day. They have demonstrated proof of principle on a simple small molecule system, glycerol in water mixture, but are not gearing up to use it to study biological macromolecules, such as proteins. Specifically, they hope to investigate amyloid beta protein present in Alzheimer’s disease as well as notorious membrane-bound proteins that are effectively off-limits to techniques such as X-ray crystallography, including ion channel proteins and rhodopsins. The team points out that the sensitivity boost means they do not require as large a sample as with earlier techniques.

Related Links

Sci Adv 2019, online: "Time-optimized pulsed dynamic nuclear polarization"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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