Don't blink

In the world of molecular dynamics, timescales are short. But by taking a series of infrared snapshots, changes in molecular configuration that occur over a few hundred picoseconds can be observed.

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Molecules are quick off the mark. Their intricate motion occurs on the order of picoseconds, and most ‘eyes’ just can’t keep up. But as Kolano and co-workers report¹, infrared spectroscopy can.

The conformational changes and vibrations of various chemical groups give us insights into how biomolecules work, telling us for example how they fold and unfold. But the problem is that such interactions are fast and produce tiny, almost immeasurable effects, which are often masked by more dominant processes.

Reporting in Nature, Kolano and colleagues find a way around this. Using a technique known as transient two-dimensional infrared spectroscopy, they watch a molecule — specifically a loop of four amino acids — unfold in solution in real time. They record two spectra: one using a ‘pump’ pulse of infrared light (which excites the molecules) and another with a ‘probe’ pulse (which maps how the excited state changes over time). By subtracting one spectrum from the other to obtain an infrared ‘difference’ spectrum, the researchers reveal the subtle, higher-order interactions within the molecule.

To trigger the molecule’s motion, the team folds up the molecule using a weak disulphide bond. By zapping this bond with ultraviolet light, it can be broken at will, causing the molecule to unfold. Femtosecond pulses of infrared light are then fired at the molecule and a series of snapshots taken as the unfolding occurs. After subtracting a reference spectrum from the transient spectra, the authors are able to observe molecular movements that occur over a few hundred picoseconds. This technique could offer unprecedented insights into molecular dynamics.