Non-Markovian modeling of protein folding.
| Autor: | Ayaz C; Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany., Tepper L; Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany., Brünig FN; Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany., Kappler J; Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, United Kingdom., Daldrop JO; Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany., Netz RR; Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany; rnetz@physik.fu-berlin.de. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Aug 03; Vol. 118 (31). |
| DOI: | 10.1073/pnas.2023856118 |
| Abstrakt: | 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 [Formula: see text] 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 agree accurately with MD results, which demonstrate 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 the 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. Competing Interests: The authors declare no competing interest. (Copyright © 2021 the Author(s). Published by PNAS.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|