Primer on NMR of Biomolecules
Discovered in 1946 by independent groups at Stanford and
Harvard Universities, nuclear magnetic resonance (NMR) refers
to the ability of atomic nuclei to reorient themselves in
a magnetic field when exposed to radiation of a particular
"resonant" frequency in the radio band.
Certain atomic nuclei ("NMR isotopes") contain charged particles
with spin, which according to Maxwell's equations, induces
a magnetic field. Though small, the magnetic "moments" of
these nuclei makes them sensitive to an external magnetic
field. In an NMR magnet, the nuclei act like tiny bar magnets
and tend to align themselves preferentially in a particular
configuration, while also undergoing spinning motions similar
to the gyroscopic precessions of bicycle wheels or spinning
tops under an external torque.
Any fluctuating magnetic field orthogonal to that of the
NMR magnet will perturb the alignment of the nuclear magnetic
moments away from the equilibrium configuration, but only
if the frequency of the fluctuating field is precisely equal
to the precession frequencies of the nuclear magnetic moments.
These are called the resonant, or Larmor, frequencies and
are proportional to the field strength of the NMR magnet.
TSRI's new 21 tesla magnet, for instance, causes protons to
precess at 900 MHz. Movement of atomic nuclei in the NMR as
they go in and out of resonance causes small but measurable
induced voltages, and it is this signal which is being measured
in the NMR experiment.
An NMR spectrometer will scan a broad range of radio frequencies
and record all the resonances as a spectrum. Atoms like 1H,
13C, or 15N, which are ubiquitous in
proteins and nucleic acids, have a nuclear spin and give rise
to NMR signals, whereas atoms like 12C and 16O
have no nuclear spin and therefore no signal. Different spectra
can be taken with molecules that have been selectively isotopically
labeled with atoms that have or do not have a spin.
In an NMR experiment, a sample in a glass tube is inserted
into the magnet, and the resonant responses of the atoms in
the sample over a range of frequencies are recorded. These
responses are influenced by the shape of the molecule in which
the atoms reside—by their proximity to other atoms in
the molecule. An NMR spectrum is unique for a particular molecule,
and the structure of a molecule can be determined from its
spectrum.
There is no question that NMR is one of the fundamental
techniques in chemistry and biology today. In recognition
of that fact, Richard R. Ernst at ETH in Zürich was awarded
the 1991 Nobel Prize for Chemistry for "the development of
the methodology of high resolution nuclear magnetic resonance
(NMR) spectroscopy"—tools that also provided a starting
platform for Wüthrich's development of NMR techniques
to study biological macromolecules.
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