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[待翻译] [FAH] Folding@home 公开发表论文列表

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 楼主| 发表于 2013-12-17 11:50:52 | 显示全部楼层
认领第 105 篇论文。

105. Effects of familial mutations on the monomer structure of Aβ₄₂
Lin YS, Pande VS.
Biophysical Journal (Dec 2012)

Aβ₄₂ 单体结构对家族性突变的影响
Lin YS, Pande VS. 发表于《Biophysical Journa》2012 年 12 月刊

SUMMARY.
概要

This details some new results from Folding@home on Alzheimer’s Disease.

本文详细介绍了 Folding@home 项目对阿尔茨海默氏病(Alzheimer’s Disease)研究取得的一些新成果。

ABSTRACT.
摘要

Amyloid beta (Aβ) peptide plays an important role in Alzheimer’s disease. A number of mutations in the Aβ sequence lead to familial Alzheimer’s disease, congophilic amyloid angiopathy, or hereditary cerebral hemorrhage with amyloid. Using molecular dynamics simulations of ∼200 μs for each system, we characterize and contrast the consequences of four pathogenic mutations (Italian, Dutch, Arctic, and Iowa) for the structural ensemble of the Aβ monomer. The four familial mutations are found to have distinct consequences for the monomer structure.

β-淀粉样肽(Amyloid beta peptide,简称 Aβ)在阿尔茨海默氏病(Alzheimer’s Disease)机理中扮演着重要的角色。一些在 Aβ 序列的突变导致家族性阿尔茨海默氏病(Alzheimer’s Disease)、脑淀粉样血管病(congophilic amyloid angiopathy)、遗传性脑出血伴淀粉样变( hereditary cerebral hemorrhage with amyloid)。对每个系统使用 ∼200 μs 时间尺度的分子动力学模拟,我们刻画和对比了四个区域(意大利、荷兰、北极地区、美国爱荷华州)的致病性突变和 Aβ 单体组合结构。四个区域的致病性突变都发现明显不同的 Aβ 单体结构。
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 楼主| 发表于 2013-12-18 08:25:28 | 显示全部楼层
认领第 104 篇论文。

104. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15.
Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R, Ozkan E, Leonard WJ, Garcia KC.
Natural Immunology (Dec 2012)

关于 IL-2 和 IL-15 功能分歧的机制和结构特点的见解

Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R, Ozkan E, Leonard WJ, Garcia KC 发表于《自然免疫学(Natural Immunology)》2012 年 12 月刊

SUMMARY.
概要

This is a continuation of paper #100, “Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’”. Our results provide new insights for the development of new specific therapeutics based on interleukin.

本篇论文是第 100 篇论文“Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’”的延续。我们的研究提供了基于白介素(interleukin)开发特异性免疫治疗的新观点。

ABSTRACT.
摘要

Interleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2Rβ and the common γ-chain (γ(c)). Here we found that in the structure of the IL-15-IL-15Rα-IL-2Rβ-γ(c) quaternary complex, IL-15 binds to IL-2Rβ and γ(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2Rα-IL-2Rβ-γ(c) complex, despite their different receptor-binding chemistries. IL-15Rα substantially increased the affinity of IL-15 for IL-2Rβ, and this allostery was required for IL-15 trans signaling. Consistent with their identical IL-2Rβ-γ(c) dimer geometries, IL-2 and IL-15 showed similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induced similar signals, and the cytokine specificity of IL-2Rα versus IL-15Rα determined cellular responsiveness. Our results provide new insights for the development of specific immunotherapeutics based on IL-15 or IL-2.

虽然白介素 15(Interleukin 15,简称 IL-15)和白介素 2(IL-2)的信号都是通过受体的 IL-2Rβ 和常见的 γ-chain(γ-链,简称 γ(c))传递,它们具有不同的免疫功能。本研究发现 IL-15–IL-15Rα–IL-2Rβ–γ(c) 四聚体复合物的结构,其中 IL-15 结合 IL-2Rβ 和 γ(c) 形成异二聚体,几乎与 IL-2–IL-2Rα–IL-2Rβ–γ(c) 复合物的结构没什么差别,尽管它们具有不同的受体结合化学反应。IL-15Rα 大幅增加 IL-15 与 IL-2Rβ 的亲和力,并且这种变构效应是 IL-15 反式信号传导所必需的。与它们完全相同的 IL-2Rβ–γ(c) 二聚体空间构型一致的是,IL-2 和 IL-15 虽然具有不同的受体亲和性,但它们在淋巴细胞中表现出相似的信号特性,没有什么不同。总之,IL-15 和 IL-2 诱导了相似的信号,IL-2Rα 与 IL-15Rα 的细胞因子特异性决定了它们的细胞响应。我们的研究提供了基于 IL-15 或 IL-2 开发特异性免疫治疗的新观点。

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备注:经搜索发现“生物文库”网站已有介绍翻译,链接在此 http://www.bioku.cn/201303/nature-immunology-interleukin2-il-2-il-15-functional-dichotomy/ ,本贴文字在“生物文库”译文基础上略有修改。

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发表于 2013-12-23 09:57:07 | 显示全部楼层
1-10归我了
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 楼主| 发表于 2013-12-30 08:35:13 | 显示全部楼层
认领第 103 篇论文。

103. Marked difference in saxitoxin and tetrodotoxin affinity for the human nociceptive voltage-gated sodium channel (Nav1.7)
Walker JR, Novick PA, Parsons WH, McGregor M, Zablocki J, Pande VS, Du Bois J.
Proceedings of the National Academy of Sciences, USA (Dec 2012)

Walker JR, Novick PA, Parsons WH, McGregor M, Zablocki J, Pande VS, Du Bois J 发表于《Proceedings of the National Academy of Sciences, USA》2012 年 12 月刊

SUMMARY.
概要

Here we use molecular dynamics and chemical informatics methods to better understand sodium channels. This is important as it has applications to developing pain medicines, whose functionality relies on interacting with these channels.

ABSTRACT.
摘要

Human nociceptive voltage-gated sodium channel (Na(v)1.7), a target of significant interest for the development of antinociceptive agents, is blocked by low nanomolar concentrations of (-)-tetrodotoxin(TTX) but not (+)-saxitoxin (STX) and (+)-gonyautoxin-III (GTX-III). These findings question the long-accepted view that the 1.7 isoform is both tetrodotoxin- and saxitoxin-sensitive and identify the outer pore region of the channel as a possible target for the design of Na(v)1.7-selective inhibitors. Single- and double-point amino acid mutagenesis studies along with whole-cell electrophysiology recordings establish two domain III residues (T1398 and I1399), which occur as methionine and aspartate in other Na(v) isoforms, as critical determinants of STX and gonyautoxin-III binding affinity. An advanced homology model of the Na(v) pore region is used to provide a structural rationalization for these surprising results.

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发表于 2013-12-30 21:54:26 | 显示全部楼层
1. Screen savers of the world, Unite!
联合起来,这个世界的屏保救星们!
Michael R. Shirts and Vijay Pande, Science 2000.

Summary: Is distributed computing a fundamental advance or simply fashionable computing? In this brief letter, we show how distributed computing can be used to tackle problems which make even supercomputers quake. Indeed, we show how distributed computing has the ability to create a supercomputer thousands of times more powerful than any existing machine, due the large number of processors on the internet (hundreds of millions) and the relatively small number of computer processors in supercomputers (thousands).
分布式计算究竟是一种普世进步还是仅仅是一种时尚?本文展示了分布式计算是如何被用来处理那些连超级计算机都感到棘手的问题。该文介绍了分布式计算是如何打造比现有超级计算机更为强大的设备的方法(超级计算机只有数千枚处理器,而分布式计算则可以拥有上万枚处理器)。
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发表于 2013-12-30 22:06:05 | 显示全部楼层
2. Mathematical Foundations of ensemble dynamics.
全局动力学的数学基础
Michael R. Shirts and Vijay Pande, Physical Review Letters (2001)

ABSTRACT: A set of parallel replicas of a single simulation can be statistically coupled to closely approximate long trajectories. In many cases, this produces nearly linear speedup over a single simulation (M times faster with M simulations), rendering previously intractable problems within reach of large computer clusters. Interestingly, by varying the coupling of the parallel simulations, it is possible in some systems to obtain greater than linear speedup. The methods are generalizable to any search algorithm with long residence times in intermediate states.
单一模拟的一系列平行复制品可以通过统计学复制被用来近似模拟长期轨迹。很多情况下,该过程能够以近似线性的方式加速单一模拟(比N次模拟要快N倍)。这样的话可以把曾经棘手的问题简化到超级计算机的性能范围内而变得可解。更有趣的是,通过调整平行模拟的复制过程,在某些系统下是可以获得超越线性的速度提升的。这些方法可以普遍的被运用在各类拥有长停留期中间态的运算法则搜索中。
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发表于 2014-1-1 10:44:11 | 显示全部楼层
3. b-Hairpin Folding Simulations in Atomistic Detail Using an Implicit Solvent Model.
有关implicit溶解模型下b-发夹折叠模拟的原子尺度细节
Bojan Zagrovic, Eric J. Sorin, and Vijay Pande, Journal of Molecular Biology (2001)

ABSTRACT: We have used distributed computing techniques and a supercluster of thousands of computer processors to study folding of the C-terminal b-hairpin from protein G in atomistic detail using the GB/SA implicit solvent model at 300 K. We have simulated a total of nearly 38 ms of folding time and obtained eight complete and independent folding trajectories. Starting from an extended state, we observe relaxation to an unfolded state characterized by non-specific, temporary hydrogen bonding. This is followed by the appearance of interactions between hydrophobic residues that stabilize a bent intermediate. Final formation of the complete hydrophobic core occurs cooperatively at the same time that the final hydrogen bonding pattern appears. The folded hairpin structures we observe all contain a closely packed hydrophobic core and proper b-sheet backbone dihedral angles, but they differ in backbone hydrogen bonding pattern. We show that this is consistent with the existing experimental data on the hairpin alone in solution. Our analysis also reveals short-lived semi-helical intermediates which denote a thermodynamic trap. Our results are consistent with a three-state mechanism with a single rate-limiting step in which a varying final hydrogen bond pattern is apparent, and semi-helical off-pathway intermediates may appear early in the folding process. We include details of the ensemble dynamics methodology and a discussion of our achievements using this new computational device for studying dynamics at the atomic level.

在300k的GB/SA implicit溶解模型下,我们利用分布式计算技术并配合使用由数千台电脑组成的集群在原子尺度上研究了C端b夹由G蛋白折叠的过程。我们模拟了近38微秒的折叠时间,并且获得了8条独立且完整的轨迹。由初始的扩展态开始,我们观察了其变为一个普通的、由氢键临时连接的非折叠态的过程。这之后,它与疏水的残存物反应并形成一个稳定的、弯曲的中间产物。疏水核心的最终形成与氢键形态的产生是同时发生的。在所有的发卡结构中,我们都观测到了一个紧密包裹的疏水核以及恰当的b-sheet核心二水合物angle(突起?角度?),不过不同的核心氢键形式有着不同的发卡结构。我们指出这与现有的实验结论一致。我们的分析还发现了一种寿命很短的半螺旋中间产物。该中间产物可以定义一种热力学陷阱。我们的结果与拥有单一rate limiting步骤的三态结构一致。该步骤中我们可观察到可变的最终氢键连接形式。在折叠早期,我们还能观察到与路径无关的半螺旋中间产物。文章中,我们会详细的通过这种新计算方法在原子尺度上研究动力学并介绍动力学方法论与成果。
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发表于 2014-1-23 09:46:11 | 显示全部楼层
4. Atomistic protein folding simulations on the submillisecond timescale using worldwide distributed computing.
Vijay Pande, et al. Peter Kollman Memorial Issue, Biopolymers (2002)

ABSTRACT: Atomistic simulations of protein folding have the potential to be a great complement to experimental studies, but have been severely limited by the time scales accessible with current computer hardware and algorithms. By employing a worldwide distributed computing network of tens of thousands of PCs and algorithms designed to efficiently utilize this new many-processor, highly heterogeneous, loosely coupled distributed computing paradigm, we have been able to simulate hundreds of microseconds of atomistic molecular dynamics. This has allowed us to directly simulate the folding mechanism and to accurately predict the folding rate of several fast-folding proteins and polymers, including a nonbiological helix, polypeptide a-helices, a b-hairpin, and a three-helix bundle protein from the villin headpiece. Our results demonstrate that one can reach the time scales needed to simulate fast folding using distributed computing, and that potential sets used to describe interatomic interactions are sufficiently accurate to reach the folded state with experimentally validated rates, at least for small proteins.

4 利用全球分布式计算对蛋白质折叠进行微秒级模拟
对蛋白质的折叠过程进行原子尺度上的模拟可能会作为实验研究的绝佳补充。但遗憾的是,模拟的时间长度受到当今计算机硬件与算法的严格制约。不过,借助全球范围内的分布式计算网络以及专门为之编写的能够高效的利用其分散、高度异构、多处理器等特性算法,我们可以对分子动力学进行数百微秒的模拟。这使得我们能够直接模拟折叠结构并且准确的预测一些能够被快速折叠的蛋白质及聚合体的折叠速率。这其中包括一种非生物螺旋,多肽键a螺旋,一种b发夹(不确定)以及一种来自villin headpiece的三螺旋聚合蛋白质。我们的结果表明科学家们可以利用分布式计算来达到快速折叠所需要的模拟时间。而且,至少对小蛋白质分子来说,用来描述原子间相互作用的候选组能够有效并准确的达到折叠态。
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发表于 2018-12-17 11:41:54 | 显示全部楼层
最后回复被广告狗污染了。。我踩踩
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发表于 2019-3-8 10:23:19 | 显示全部楼层
最后回复被广告狗污染了。。我踩踩
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发表于 2019-3-9 01:59:54 | 显示全部楼层
也是一个很不错的项目了。可惜。
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发表于 2019-3-13 10:52:57 | 显示全部楼层
wuhongyi 发表于 2019-3-9 01:59
也是一个很不错的项目了。可惜。

可惜啥??
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发表于 2019-6-10 09:04:54 | 显示全部楼层

就 一直没有更新下去 有空我看看要不要再找找
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