Title:
Exploring the locking stage of NFGAILS amyloid fibrillation via transition manifold analysis
Author(s):
Bittracher, Andreas; Moschner, Johann; Koksch, Beate; Netz, Roland; Schütte, Christof
Year of publication:
2021
Available Date:
2021-12-02T08:05:28Z
Abstract:
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.
Part of Identifier:
e-ISSN (online): 1434-6036
Keywords:
transition manifold analysis
NFGAILS amyloid fibrillation
locking stage
DDC-Classification:
570 Biowissenschaften; Biologie
Publication Type:
Wissenschaftlicher Artikel
URL of the Original Publication:
DOI of the Original Publication:
Journaltitle:
The European Physical Journal B
Department/institution:
Mathematik und Informatik
Biologie, Chemie, Pharmazie
Physik
Institut für Mathematik
Institut für Chemie und Biochemie
Comments:
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin gefördert.