Distinct oligomerization and fibrillization dynamics of amyloid core sequences of amyloid-beta and islet amyloid polypeptide

Literature Information

Publication Date 2017-10-11
DOI 10.1039/C7CP05695H
Impact Factor 3.676
Authors

Yunxiang Sun, Bo Wang, Xinwei Ge, Feng Ding


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Abstract

A direct observation of amyloid aggregation from isolated peptides to cross-β fibrils is crucial for understanding the nucleation-dependence process, but the corresponding macroscopic timescales impose a major computational challenge. Using rapid all-atom discrete molecular dynamics simulations, we capture the oligomerization and fibrillization dynamics of the amyloid core sequences of amyloid-β (Aβ) in Alzheimer's disease and islet amyloid polypeptide (IAPP) in type-2 diabetes, namely Aβ16–22 and IAPP22–28. Both peptides and their mixture spontaneously assemble into cross-β aggregates in silico, but follow distinct pathways. Aβ16–22 is highly aggregation-prone with a funneled free energy basin toward multi-layer β-sheet aggregates. IAPP22–28, on the other hand, features the accumulation of unstructured oligomers before the nucleation of β-sheets and growth into double-layer β-sheet aggregates. In the presence of Aβ16–22, the aggregation of IAPP22–28 is promoted by forming co-aggregated multi-layer β-sheets. Our study offers a detailed molecular insight to the long-postulated oligomerization-nucleation process in the amyloid aggregations.

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Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics
CiteScore: 5.5
Self-citation Rate: 10.3%
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Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.

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