ArticleJournal of the American Chemical Society2014
Fibril elongation by Aβ(17-42): kinetic network analysis of hybrid-resolution molecular dynamics simulations.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 129 citations in OpenAlex.
- Efficient and accurate binding free energy calculation of AβProteins · 2025Article
- Exploring Abeta42 monomer diffusion dynamics on fibril surfaces through molecular simulations.Protein science : a publication of the Protein Society · 2025Article
- Survey of the Aβ-peptide structural diversity: molecular dynamics approaches.Biophysical reviews · 2024Review
- Peptide Self-Assembly into Amyloid Fibrils: Unbiased All-Atom Simulations.The journal of physical chemistry. B · 2024Review
- Growth kinetics of amyloid-like fibrils: An integrated atomistic simulation and continuum theory approach.PNAS nexus · 2024Article
- Nucleation and Growth of Amyloid Fibrils.The journal of physical chemistry. B · 2023Article
- Direct Observation of Seeded Conformational Conversion of hIAPPJournal of chemical information and modeling · 2023Article
- EGCG-Mediated Protection of Transthyretin Amyloidosis by Stabilizing Transthyretin Tetramers and Disrupting Transthyretin Aggregates.International journal of molecular sciences · 2023Article
- The α-Synuclein Monomer May Have Different Misfolding Mechanisms in the Induction of α-Synuclein Fibrils with Different Polymorphs.Biomolecules · 2023Article
- Molecular Dynamics Simulation Studies on the Aggregation of Amyloid-β Peptides and Their Disaggregation by Ultrasonic Wave and Infrared Laser Irradiation.Molecules (Basel, Switzerland) · 2022Review
- Mechanistic Kinetic Model Reveals How Amyloidogenic Hydrophobic Patches Facilitate the Amyloid-β Fibril Elongation.ACS chemical neuroscience · 2022Article
- Single-molecule fluorescence imaging and deep learning reveal highly heterogeneous aggregation of amyloid-β 42.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Anatomy and formation mechanisms of early amyloid-β oligomers with lateral branching: graph network analysis on large-scale simulations.Chemical science · 2022Article
- Challenges and frontiers of computational modelling of biomolecular recognition.QRB discovery · 2022Article
- Role of TM3 in claudin-15 strand flexibility: A molecular dynamics study.Frontiers in molecular biosciences · 2022Article
- Molecular dynamics simulations of amyloid-β peptides in heterogeneous environments.Biophysics and physicobiology · 2022Article
- Molecular dynamics study of water channels in natural and synthetic amyloid-β fibrils.The Journal of chemical physics · 2021Article
- Multiscale Models for Fibril Formation: Rare Events Methods, Microkinetic Models, and Population Balances.Life (Basel, Switzerland) · 2021Article
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
- Promotion and Inhibition of Amyloid-β Peptide Aggregation: Molecular Dynamics Studies.International journal of molecular sciences · 2021Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
A critical step of β-amyloid fibril formation is fibril elongation in which amyloid-β monomers undergo structural transitions to fibrillar structures upon their binding to fibril tips. The atomic detail of the structural transitions remains poorly understood. Computational characterization of the structural transitions is limited so far to short Aβ segments (5-10 aa) owing to the long time scale of Aβ fibril elongation. To overcome the computational time scale limit, we combined a hybrid-resolution model with umbrella sampling and replica exchange molecular dynamics and performed altogether ∼1.3 ms of molecular dynamics simulations of fibril elongation for Aβ17-42. Kinetic network analysis of biased simulations resulted in a kinetic model that encompasses all Aβ segments essential for fibril formation. The model not only reproduces key properties of fibril elongation measured in experiments, including Aβ binding affinity, activation enthalpy of Aβ structural transitions and a large time scale gap (τlock/τdock = 10(3)-10(4)) between Aβ binding and its structural transitions, but also reveals detailed pathways involving structural transitions not seen before, namely, fibril formation both in hydrophobic regions L17-A21 and G37-A42 preceding fibril formation in hydrophilic region E22-A30. Moreover, the model identifies as important kinetic intermediates strand-loop-strand (SLS) structures of Aβ monomers, long suspected to be related to fibril elongation. The kinetic model suggests further that fibril elongation arises faster at the fibril tip with exposed L17-A21, rather than at the other tip, explaining thereby unidirectional fibril growth observed previously in experiments.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.