Protein folding is a central puzzle of biophysics. A linear chain of hundreds or thousands of amino acids quickly and reliably winds its way into a preordained three-dimensional shape. Yet despite decades of research, it’s not fully understood just how that happens, nor is it possible to predict a protein’s final structure from its amino-acid sequence. Solving the mystery could enable the design of artificial proteins from scratch. It could also facilitate cures for the many diseases associated with proteins misfolding into the wrong structure.
Some things are known: On the way to its final folded structure, the molecule hops among metastable, partially folded intermediates. The metastable configurations, which typically persist for tens to hundreds of milliseconds, are relatively easy to study experimentally. But the hops between them, which may harbor important clues about how proteins are guided to the correct structure, last only microseconds and are much trickier to...
