Analysing biochemical interactions in action
It’s difficult to predict someone’s journey from where they start and finish, unless you know what guided their route. The same is true for biological molecules, but here structural biologists piece together an important microscopic timeline – when a RYR1 receptor binds to its ligand – like a lock and key that opens a door-like channel into muscle cells. The researchers know the receptor’s movements leave a sort of trail as its ‘energy state’ changes. They use computer algorithms to map a likely path across two energy landscapes (right) – before (top) and after (bottom) the ligand binds. The receptor starts off 'cold' on the top map, passing through an energetic 'hotspot' where the ligand begins to attach, then flips to the bottom map where it becomes cold again. Matching this timeline to cryo-electron microscopy pictures creates a movie of the shape-shifting receptor (left) – and could retrace the steps of other molecules too.
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