Understanding the Twisted Structure of Amyloid Fibrils via Molecular Simulations

Journal Article · Tue Aug 14 04:00:00 EDT 2018 · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry

DOI:https://doi.org/10.1021/acs.jpcb.8b07255· OSTI ID:1565745

Lu, Lu ^[1]; Deng, Yixiang ^[2]; Li, Xuejin ^[1]; Li, He ^[1]; Karniadakis, George Em ^[1]

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1. Division of Applied Mathematics, Brown University, Providence, Rhode Island 02912, United States
2. School of Engineering, Brown University, Providence, Rhode Island 02912, United States

According to the article, accumulation and aggregation of amyloid are associated with the pathogenesis of many human diseases, such as Alzheimer’s disease and Type 2 diabetes mellitus. Therefore, a quantitative understanding of the molecular mechanisms causing different aggregated structures and biomechanical properties of amyloid fibrils could shed some light into the progression of these diseases. In this work, we develop coarse-grained molecular dynamics (CGMD) models to simulate the dynamic self-assembly of two types of amyloids (amylin and amyloid β (Aβ)). We investigate the structural and mechanical properties of different types of aggregated amyloid fibrils. Our simulations demonstrate that amyloid fibrils could result from longitudinal growth of protofilament bundles, confirming one of the hypotheses on the fibril formation. In addition, we find that the persistence length of amylin fibrils increases concurrently with their pitch length, suggesting that the bending stiffness of amylin fibrils becomes larger when the amylin fibrils are less twisted. Similar results are observed for Aβ fibrils. These findings quantify the connection between the structural and the biomechanical properties of the fibrils. The CGMD models developed in this work can be potentially used to examine efficacy of anti-aggregation drugs, which could help in developing new treatments.

• Research Organization: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); Argonne National Lab. (ANL), Argonne, IL (United States); UT-Battelle LLC/ORNL, Oak Ridge, TN (Unted States)
• Sponsoring Organization: USDOE Office of Science
• DOE Contract Number: AC02-06CH11357; AC05-00OR22725
• OSTI ID: 1565745
• Journal Information: Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry, Journal Name: Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry Journal Issue: 49 Vol. 122; ISSN 1520-6106
• Publisher: American Chemical Society
• Country of Publication: United States
• Language: English

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Chemistry