https://doi.org/10.1140/epjb/s10051-021-00200-0
Regular Article - Computational Methods
Exploring the locking stage of NFGAILS amyloid fibrillation via transition manifold analysis
1
Department of Mathematics, Freie Universität Berlin, Berlin, Germany
2
Department of Chemistry, Freie Universität Berlin, Berlin, Germany
3
Department of Physics, Freie Universität Berlin, Berlin, Germany
4
Zuse Institute Berlin, Berlin, Germany
Received:
13
April
2021
Accepted:
7
September
2021
Published online:
30
September
2021
We demonstrate the application of the transition manifold framework to the late-stage fibrillation process of the NFGAILS peptide, a amyloidogenic fragment of the human islet amyloid polypeptide (hIAPP). This framework formulates machine learning methods for the analysis of multi-scale stochastic systems from short, massively parallel molecular dynamical simulations. We identify key intermediate states and dominant pathways of the process. Furthermore, we identify the optimally timescale-preserving reaction coordinate for the dock-lock process to a fixed pre-formed fibril and show that it exhibits strong correlation with the mean native hydrogen-bond distance. These results pave the way for a comprehensive model reduction and multi-scale analysis of amyloid fibrillation processes.
Supplementary Information The online version contains supplementary material available at https://doi.org/10.1140/epjb/s10051-021-00200-0.
© The Author(s) 2021
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