To transform from linear chains to three-dimensional structures, in vivo proteins somehow navigate tortuous free-energy landscapes. Their final configurations must be just right for them to function properly; protein misfolding is thought to underlie some allergies as well as neurodegenerative diseases such as Parkinson’s and Alzheimer’s.
X-ray crystallography and NMR are well-established methods for accessing the detailed structure of a protein’s final folded configuration. Gathering dynamical information about the folding process itself requires real-time techniques such as fluorescence, circular dichroism, and hydrogen exchange; acquiring information that quickly, however, comes at the expense of structural detail. Molecular dynamics simulations are also a valuable tool for studying protein configurations (see Physics Today, December 2013, page 13), but because of computational limitations they fail to capture either the complete atomistic detail of real proteins or the complete process of folding.
Now Jaekyun Jeon, Robert Tycko, and coworkers at the National Institutes...
