We extract the folding free-energy landscape and the time-dependent friction function, the two ingredients of the generalized Langevin equation (GLE), from explicit-water molecular dynamics (MD) simulations of the α-helix forming polypeptide Alanine9 for a one-dimensional reaction coordinate based on the sum of the native H-bond distances. Folding and unfolding times from numerical integration of the GLE for the reaction coordinate agree accurately with MD results, which demonstrates the robustness of our GLE-based non-Markovian model. In contrast, Markovian models do not accurately describe the peptide kinetics and in particular cannot reproduce the folding and unfolding kinetics simultaneously, even if a spatially dependent friction profile is used. Analysis of the GLE demonstrates that memory effects in the friction significantly speed up peptide folding and unfolding kinetics, as predicted by Grote-Hynes theory, and are the cause of anomalous diffusion in configuration space. Our methods are applicable to any reaction coordinate and in principle also to experimental trajectories from single-molecule experiments. Our results demonstrate that a consistent description of protein folding dynamics must account for memory friction effects.
