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Experimental evidence suggests that the folding and aggregation of the amyloid $\beta$-protein (A$\beta$) into oligomers is a key pathogenetic event in Alzheimer's disease (AD). Inhibiting the pathologic folding and oligomerization of…

生物大分子 · 定量生物学 2009-11-11 Luis Cruz , Brigita Urbanc , Jose M. Borreguero , Noel D. Lazo , David B. Teplow , H. Eugene Stanley

The amyloid $\beta$ peptide (A$\beta$42), whose aggregation is associated with Alzheimer's disease, is an amphiphatic peptide with a high propensity to self-assemble. A$\beta$42 has a net negative charge at physiological pH and modulations…

分子网络 · 定量生物学 2020-08-25 Georg Meisl , Xiaoting Yang , Christopher M. Dobson , Sara Linse , Tuomas P. J. Knowles

Inspired by recent suggestions that the Alzheimer's amyloid beta peptide (A beta) can insert into cell membranes and form harmful ion channels, we model insertion of the 40 and 42 residue forms of the peptide into cell membranes using a…

Recent experiments with amyloid-beta (Abeta) peptide suggest that formation of toxic oligomers may be an important contribution to the onset of Alzheimer's disease. The toxicity of Abeta oligomers depends on their structure, which is…

生物物理 · 物理学 2009-11-10 B. Urbanc , L. Cruz , F. Ding , D. Sammond , S. Khare , S. V. Buldyrev , H. E. Stanley , N. V. Dokholyan

The 16-22 amino acid fragment of the beta-amyloid peptide associated with the Alzheimer's disease, Abeta, is capable of forming amyloid fibrils. Here we study the aggregation mechanism of Abeta(16-22) peptides by unbiased thermodynamic…

生物大分子 · 定量生物学 2009-11-10 Giorgio Favrin , Anders Irbäck , Sandipan Mohanty

In this study, we investigate interactions of extended conformations of homodimeric peptides made of small (glycine or alanine) and large hydrophobic (valine or leucine) sidechains using all-atom molecular dynamics simulations to decipher…

生物物理 · 物理学 2015-06-17 Chitra Narayanan , Cristiano L. Dias

Exploring the protein-folding problem has been a long-standing challenge in molecular biology. Protein folding is highly dependent on folding of secondary structures as the way to pave a native folding pathway. Here, we demonstrate that a…

生物大分子 · 定量生物学 2020-09-17 Jiacheng Li , Xiaoliang Ma , Hongchi Zhang , Chengyu Hou , Liping Shi , Shuai Guo , Chenchen Liao , Bing Zheng , Lin Ye , Lin Yang , Xiaodong He

Effects of the mismatch between the hydrophobic length, d, of transmembrane alpha helices of integral proteins and the hydrophobic thickness, D_h, of the membranes they span are studied theoretically utilizing a microscopic model of lipids.…

软凝聚态物质 · 物理学 2009-11-07 Daniel Duque , Xiao-jun Li , Kirill Katsov , Michael Schick

The formation of amyloid fibrils comprising amyloid $\beta$ (A$\beta$) peptides is associated with the pathology of Alzheimer's disease. In this study, we theoretically investigated the A$\beta$ structure at the fibril end using the density…

Pathological folding and oligomer formation of the amyloid beta-protein (Abeta) are widely perceived as central to Alzheimer's disease (AD). Experimental approaches to study Abeta self-assembly are problematic, because most relevant…

生物大分子 · 定量生物学 2009-11-13 Sijung Yun , Brigita Urbanc , Luis Cruz , Gal Bitan , David B. Teplow , H. Eugene Stanley

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that severely impairs survival and quality of life. While anti-amyloid beta (Abeta) therapies can slow disease progression, their efficacy depends on personalized dosing…

最优化与控制 · 数学 2025-11-10 Sun Lee , Chiu-Yen Kao , Zhiyuan Li , Tingting Dan , Guorong Wu , Wenrui Hao

Motivated by the biologically important and complex phenomena of A\beta\ peptide aggregation in Alzheimer's disease, we introduce a model and simulation methodology for studying protein aggregation that includes extra-cellular aggregation,…

定量方法 · 定量生物学 2018-03-02 Youval Dar , Benjamin Bairrington , Daniel Cox , Rajiv Singh

The behavior of proteins near interfaces is relevant for biological and medical purposes. Previous results in bulk show that, when the protein concentration increases, the proteins unfold and, at higher concentrations, aggregate. Here, we…

软凝聚态物质 · 物理学 2021-01-19 David March , Valentino Bianco , Giancarlo Franzese

Relatively short peptides, such as toxins and antimicrobial-peptides, are known to insert themselves into cell membranes. On the basis of simple bead-spring models for the membrane lipids, the peptide, and water, detailed processes of the…

软凝聚态物质 · 物理学 2007-05-23 Mitsuharu Okazaki , Tomoki Watanabe , Naohito Urakami , Takashi Yamamoto

It is known that steric blocking by peptide sidechains of hydrogen bonding, HB, between water and peptide groups, PGs, in beta sheets accords with an amino acid intrinsic beta sheet preference. The present observations with Quantum…

化学物理 · 物理学 2016-10-04 John N. Sharley

Amyloid beta peptides (A\b{eta}), implicated in Alzheimers disease (AD), interact with the cellular membrane and induce amyloid toxicity. The composition of cellular membranes changes in aging and AD. We designed multi component lipid…

生物物理 · 物理学 2017-11-01 Elizabeth Drolle , Alexander Negoda , Keely Hammond , Evgeny Pavlov , Zoya Leonenko

Zinc is found saturated in the deposited Amyloid-beta (AB) peptide plaques in brains of patients subjected to Alzheimer disease (AD). Zinc binding to AB promotes aggregations, including the toxic soluble AB species. Up to now, only the…

生物大分子 · 定量生物学 2013-01-09 Yandong Huang , Jianwei Shuai

The determination of the folding mechanisms of proteins is critical to understand the topological change that can propagate Alzheimer and Creutzfeld-Jakobs diseases, among others. The computational community has paid considerable attention…

生物大分子 · 定量生物学 2007-05-23 Guanghong Wei , Normand Mousseau , Philippe Derreumaux

The link between metals, Alzheimers disease (AD) and its implicated protein, amyloid \b{eta} (A\b{eta}), is complex and highly studied. AD is believed to occur as a result of the misfolding and aggregation of A\b{eta}. The dyshomeostasis of…

生物物理 · 物理学 2017-04-28 Francis Hane , Gary Tran , Simon Attwood , Zoya Leonenko

We study the aggregation of peptides using the discrete molecular dynamics simulations. At temperatures above the alpha-helix melting temperature of a single peptide, the model peptides aggregate into a multi-layer parallel beta-sheet…

软凝聚态物质 · 物理学 2009-11-10 S. Peng , F. Ding , B. Urbanc , S. V. Buldyrev , L. Cruz , H. E. Stanley , N. V. Dokholyan
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