Fantastical Fridays: NMR Goes Natural, Baby!

There are a number of approaches scientists take to get at the fundamental nature of life, and one of those is elucidating the chemical structures of the molecules that make life happen, particularly proteins, which are the workhorses of the cell. One of the two primary methods for determining these structures is nuclear magnetic resonance (NMR) and the other is x-ray crystallography. My current work is in the former, meaning I spend a lot of time sitting in front of a huge magnet and even more time staring at a computer screen trying to make sense of the data I get from the magnet. As people in the field continue to try to build bigger and bigger magnets to acquire better NMR data, though, one group reported earlier this year in Nature Physics that sometimes it may be better to just go natural. Forget about all of the high-tech magnets--just use the big one right under your feet!

One's small, but fierce. The other has bulk, but lacks strength. Let the battle begin!

..........vs..........

Note: the fundamentals of NMR are a subject for another post, but, in short, here's how it works. Each protein is made up of thousands of atoms organized in a specific three-dimensional conformation, and each of those atoms has a nucleus with a magnetic moment. Normally, the magnetic moments of these nuclei are arranged randomly, but within a strong magnetic field they all line up. When a nucleus absorbs radio waves, though, its magnetic moment will spin around in a circle, in turn emitting its own radio waves, which can be detected. A given type of atom (hydrogen, nitrogen, carbon, etc.) will emit radio waves at a characteristic frequency. However, this frequency will vary slightly depending on the chemical environment that a particular atom is in. Scientists can use this difference, called a "chemical shift", to obtain valuable structural information about a protein (or any other type of molecule). The stronger the magnet is, the larger the observed chemical shifts, so bigger and better magnets are constantly being developed.

In NMR, bigger really is better, at least when it comes to magnetic field strength, and the entire field has in some ways become one big manhood size-measuring contest. (A contest, I should add, that the lab I'm in is currently winning, with our new 22.3 Tesla (950 MHz) magnet, which is the most powerful NMR magnet in the world.... OK, I'll admit that it kind of sounds like there might be some deep-seated issues at play here....) These high field magnets, though, are incredibly complex and expensive, relying on advanced superconductor technology to stably generate such a strong magnetic field.

In the February 2006 issue of Nature Physics, a team led by Stephan Appelt of Jülich research center demonstrated that sometimes may have provided us with the best NMR machine of all, the Earth. While the Earth is literally a much bigger than any magnet humans have ever built, it's several orders of magnitude weaker than the magnets routinely used in NMR. For example, our new 22.3 Tesla machine generates a field roughly 500,000 times stronger than the magnetic field of the Earth. The group from Jülich, though, showed that for certain application, the Earth's magnetic field actually yields better results.

So, how did they manage to get better results from a much weaker magnetic field? There are two reasons. Firstly, although the Earth's magnetic field is weak, it is remarkably homogeneous compared to the field generated by an NMR magnet. As anyone who has worked with NMR will surely attest to, one of the most frustrating and time-consuming parts of setting up any NMR experiment is a process called shimming, which involves tediously adjusting several smaller magnets around the main magnet to correct for inconsistencies in the magnetic field. The reason for all of this effort is that a more homogeneous field yields better results.

The second reason for the utility of the Earth's magnetic field in NMR stems from the fact that the environment outside of an NMR machine, particularly the presence of metal objects, can influence the results of an experiment. Although a normal NMR machine is stationary, since this particular study didn't need a superconducting magnet, these scientists were able to build a portable NMR machine that they could use to perform their experiments far from the complications that arise from civilization and its metallic infrastructure. In this case, they were studying J-coupling, one of the many phenomena observable by NMR. Since J-couplings are particularly sensitive to these outside influences, the authors obtained better results from the Earth's magnetic field than from superconducting magnets.

So, do we need to demand to get our money back for our new huge and expensive magnet? Not at all. The scientists at Jülich were studying J-couplings, which are not dependent on the field strength. In contrast, protein NMR, the work we do in our lab, is very dependent on measuring chemical shifts, which do depend on field strength. For example, let's say we're looking at the peaks from two hydrogen atoms in an NMR spectrum acquired on the 22.3 Tesla machine, and they're separated by 450 Hz. In this spectrum, we will easily see these two peaks as distinct and separate. If we were looking at the same spectrum obtained from the Earth's magnetic field (about 0.00005 Tesla), these two peaks would only be separated by 0.001 Hz, making them virtually indistinguishable. So, the findings of this study won't be transforming protein NMR anytime soon.

Still, after spending long hours hiding away in the basement of our building with only the very expensive company of a few NMR machines, I find the idea of performing NMR experiments and being able to reconnect with nature at the same time undeniably appealing.

Stephan Appelt, Holger Kuhn, F. Wolfgang Hasing and Bernhard Blumich, Chemical analysis by ultrahigh-resolution nuclear magnetic resonance in the Earth's magnetic field, Nature Physics 2 (2006), 105-9.