Protein folding trajectories can be described quantitatively by one-dimensional diffusion over measured energy landscapes

• Published in: Nature physics 2016-07, Vol.12 (7), p.700-703
• Main Authors: Neupane, Krishna, Manuel, Ajay P., Woodside, Michael T.
• Format: Article
• Language: English
• Subjects: 631/57/2265; 639/766/747; Atomic; Biophysics; Classical and Continuum Physics; Coiling; Complex Systems; Condensed Matter Physics; Diffusion; Energy; Folding; Kinetics; Landscapes; letter; Mathematical analysis; Mathematical and Computational Physics; Molecular; Molecules; Optical and Plasma Physics; Physics; Protein folding; Proteins; Searching; Theoretical; Trajectories
• ISSN: 1745-2473; 1745-2481
• DOI: 10.1038/nphys3677

Multidimensional protein-folding dynamics are often probed experimentally by projecting into a single dimension. Single-molecule experiments now verify the idea that folding can be understood in terms of one-dimensional diffusion over a landscape. Protein folding features a diffusive search over a multidimensional energy landscape in conformational space for the minimum-energy structure 1 . Experiments, however, are usually interpreted in terms of a one-dimensional (1D) projection of the full landscape onto a practical reaction coordinate. Although simulations have shown that folding kinetics can be described well by diffusion over a 1D projection 2 , 3 , 1D approximations have not yet been fully validated experimentally. We used folding trajectories of single molecules held under tension in optical tweezers to compare the conditional probability of being on a transition path 4 , calculated from the trajectory 5 , with the prediction for ideal 1D diffusion over the measured 1D landscape 6 , calculated from committor statistics 7 , 8 . We found good agreement for the protein PrP (refs  9 , 10 ) and for one of the structural transitions in a leucine-zipper coiled-coil 11 , but not for a second transition in the coiled-coil, owing to poor reaction-coordinate quality 12 . These results show that 1D descriptions of folding can indeed be good, even for complex tertiary structures. More fundamentally, they also provide a fully experimental validation of the basic physical picture of folding as diffusion over a landscape.