To figure out how the atoms are connected in an unknown molecule, chemists have a suite of spectroscopic techniques at their disposal. But those techniques aren’t always well suited to proteins and other large, complicated biomolecules. Whereas the spectrum of a small molecule might consist of a few discrete, informative peaks, a typical biomolecular spectrum is an impenetrable forest of overlapping spectral lines that are nearly impossible to interpret.
Decades ago, NMR spectroscopists realized that they could obtain more informative spectra by plotting the spectral signal as a function of two frequency variables rather than one. The expansion to two dimensions not only makes the peaks easier to resolve by spreading them over a larger space, it yields information not present in a one-dimensional spectrum—for example, the off-diagonal peaks can represent signals from nearby parts of the molecule. Well-designed 2D NMR experiments can resolve the structures of full proteins (see Physics Today, October 2016, page 19).
Now Marina Edelson-Averbukh of Imperial College London and her colleagues have turned the 2D approach to a different analytical method: mass spectrometry. To take a mass spectrum, researchers ionize a sample of identical molecules and send them through an electric or magnetic field to measure their mass-to-charge ratio. The ionized molecules can be broken into fragments, whose masses then also show up in the mass spectrum and reveal bits of information about the molecular structure. For example, a peak at the mass of a carbon atom plus three hydrogen atoms is good evidence that those atoms were bound together in the original molecule. But the larger and more complicated the molecule, the less useful such insights become.