NMR analyzes protein as it folds

Abstract

Researchers have long wanted to better understand the way an unfolded protein chain reaches its final folded structure. But experimental tools needed to probe this complex process have been limited. An apparatus developed by Philip Anfinrud, Ad Bax, and coworkers at the National Institutes of Health now opens a new window on the process by allowing nuclear magnetic resonance spectroscopy to follow protein folding at an atomic level of detail in real time (Proc. Natl. Acad. Sci. USA 2018, DOI: 10.1073/pnas.1803642115). Proteins unfold when subjected to high pressure and then refold when normal pressure is restored, a handy trick that researchers pair with spectroscopic techniques to track folding. Fluorescence spectroscopy has been used in this way, but it provides only low-resolution information. NMR can obtain highly precise data at every atom position that naturally contains or can be endowed with a magnetic isotope, like hydrogen-1, carbon-13, or nitrogen-15. But NMR