The World's Most Powerful NMR Magnet Arrives at TSRI
By Jason Socrates Bardi
The largest nuclear magnetic resonance (NMR) magnet ever
constructed arrived last week at The Scripps Research Institute
(TSRI), where it was assembled into the most sensitive NMR
instrument on the planet.
The new NMR, referred to by its maximum radio frequency,
900 MHz, is now the centerpiece of TSRI's premier collection
of NMR instruments.
"It's fantastic," says Peter Wright, professor and chair
of the Department of Molecular Biology. "The capabilities
of this instrument take us to a new level."
Now in its permanent home in one corner of the Buddy Taub
Center for Molecular Structure and Design, the 900 MHz instrument
sits next to the 800 MHz instrument that has been in the same
building since 1998. Although appearing only a little taller
and a little fatter than the 800, the 900 represents a major
breakthrough in technology.
"It's rather a technological triumph," says Associate Professor
Jane Dyson of the new machine.
The instrument, which is the first of its kind and has been
several years in the making by its German manufacturer, Bruker
Instruments, Inc., is currently being cooled down to its operating
temperature of 2 degrees Kelvin above absolute zero with 5000
liters of nitrogen and up to 4,500 liters of liquid helium.
The instrument's magnet is actually several miles of ultra-high
technology Niobium-Tin and Niobium-Titanium superconducting
coils sitting directly in the helium bath, which is surrounded
by a vacuum dewar and a liquid nitrogen bath.
This magnet will be charged with over two hundred amperes
of persistent super-conducting current. Through induction,
this current will produce a stable magnetic field of 21 tesla,
which is very large compared to a hospital MRI 2 tesla magnet.
In addition, the field is remarkably homogenous: better than
one part per billion over a couple of cubic centimeters volume.
Once filled and charged, the instrument will be calibrated,
tested for a few weeks, then put to use by research groups
Improvements to Resolution and Sensitivity
"There are already problems waiting to go into it," says
Wright. "Instantlyas soon as it's available."
Some of those problems will take advantage of the improvements
of the 900 over existing lower field instruments at TSRI.
For instance, the 900 is expected to be 40 to 50 percent more
sensitive (peak heights) and have greater resolving power
(peak separations) than the 800 MHz instrument.
The increased resolution will help separate peaks of two
close chemical shifts that would normally overlap. "The first
thing we do will probably be to exploit this resolution to
study systems that were not possible before," says Dyson.
The increased sensitivity should allow measurements to be
taken on samples with lower protein concentrations. Typically,
some proteins, big and small, don't behave well at high concentrations.
Modern experiments require the protein to be stable around
100 ÁM to1mM, for instance, but this is impossible for some
systems because the molecules may dimerize, aggregate, or
precipitate at that concentration.
The concentration can be reduced but only at the cost of
reducing the signal-to-noise ratio, with the risk of losing
the signal altogether. But the increased sensitivity of the
900 should allow concentrations to be lowered even further
before the signal disappears.
However, even with the increased resolution and sensitivity,
many interesting systems remain elusive to NMR because they
are either too big, too insoluble, or too complicated. The
size limitations for structures that may be obtained through
conventional NMR, for instance, is around 30 to 40 kD, but
many proteins are simply much larger than this.
Membrane proteins are also complicated to deal with. These
proteins, which make up about one third of all the genes in
the human genome, are notoriously hard to crystallize and
would make excellent problems for NMR spectroscopists if they
weren't so large and insoluble.
Then there are partially folded and unfolded systems that
are too complicated to study with conventional NMR because
the increased flexibility of the unfolded polypeptides significantly
increases the difficulty of analyzing the spectra. Much can
be gained by studying the partly folded states of proteins
and observing how they fold. Do they make secondary or tertiary
structures? How flexible are their backbones and how flexible
are their side chains?
"All these things we can get at," she says, "but because
the spectra are so overlapped, we need this big machine."
"Until now we haven't had the tools to study these thingsthe
unfolded proteins, the membrane proteins, the huge proteinsyou
can't look at them because they are so difficult," says Dyson.
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