Reduction of All-Atom Protein Folding Dynamics to One-Dimensional Diffusion

Theoretical models have often modeled protein folding dynamics as diffusion on a low-dimensional free energy surface, a remarkable simplification. However, the accuracy of such an approximation and the number of dimensions required were not clear. For all-atom folding simulations of ten small proteins in explicit solvent we show that the folding dynamics can indeed be accurately described as diffusion on just a single coordinate, the fraction of native contacts (<i>Q</i>). The diffusion models reproduce both folding rates, and finer details such as transition-path durations and diffusive propagators. The <i>Q</i>-averaged diffusion coefficients decrease with chain length, as anticipated from energy landscape theory. Although the <i>Q</i>-diffusion model does not capture transition-path durations for the protein NuG2, we show that this can be accomplished by designing an improved coordinate <i>Q</i>_opt. Overall, one-dimensional diffusion on a suitable coordinate turns out to be a remarkably faithful model for the dynamics of the proteins considered