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[已完成翻译] [Rosetta@home]量身定做蛋白质 Proteins made to order

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发表于 2012-11-18 23:48:32 | 显示全部楼层 |阅读模式
本帖最后由 昂宿星团人 于 2013-2-17 12:37 编辑

来源:http://www.nature.com/news/proteins-made-to-order-1.11767
标题:Proteins made to order
概要:rosetta相关,介绍了用 Rosetta@home 来进行全新的蛋白质结构设计。
(有愿意帮助翻译的,请直接回帖(可以先占座,再翻译或编辑)


原文:

Proteins made to order
Researchers design proteins from scratch with predictable structures.
07 November 2012
Proteins are an enormous molecular achievement: chains of amino acids that fold spontaneously into a precise conformation, time after time, optimized by evolution for their particular function. Yet given the exponential number of contortions possible for any chain of amino acids, dictating a sequence that will fold into a predictable structure has been a daunting task.                                                                                                                                                                                                        
Now researchers report that they can do just that. By following a set of rules described in apaper published in Nature today1, a team from David Baker’s laboratory at the University of Washington in Seattle has designed five proteins from scratch that fold reliably into predicted conformations. In a blind test, the team showed that the synthesized proteins closely match the predicted structures.
“There’s really only one previous example of a protein that has been designed from scratch: that’s Top7 which we designed 10 years ago2,” said Baker, a computational structural biologist. “Top7 was sort of a one-off case,” he says. In the new work, the team presents a generalized approach.
“What you have now is a flexible set of building blocks for nanoscale assembly,” says Jeremy England, a molecular biophysicist at the Massachusetts Institute of Technology in Cambridge, who was not involved in the work.
(图)
The 3-dimensional structure of a protein is intimately related to its function.               
PASIEKA/SCIENCE PHOTO LIBRARY

Bending rules
The work was spearheaded by husband-and-wife team Nobuyasu Koga and Rie Tatsumi-Koga, protein engineers in Baker’s group. After observing the backbone structures of thousands of proteins, they developed some intuitive rules they wanted to test.
Protein strands typically form helices and other classic secondary structures that in turn fold into the final protein shape. The team realized that these structures could be made to twist in one direction or another depending on the length of the loops that connected them. By choosing the right sequence lengths between these building blocks, the team could predict which way they would fold.
Using these and additional criteria, the team developed a number of candidate sequences designed to fold into one of five structures. They vetted these sequences using the group’s Rosetta@home program, which uses volunteers’ home computer power to run protein-folding simulations. Rosetta volunteers test-folded each sequence hundreds of thousands of times. About 10% of the sequences had predicted structures that were stable and matched what the team intended. The winning sequences did not match any known natural proteins.

Platonic proteins
The team synthesized these proteins and sent them to Gaetano Montelione of Rutgers University in Piscataway, New Jersey, who determined the proteins’ structures by nuclear magnetic resonance (NMR) imaging without having seen the predicted structures. Then they compared the two versions. “It is remarkable how well the predicted structures agree with the high-quality NMR structures,” Montelione says.
Baker's proteins are in a sense “platonic ideals”, he says: simple backbone constructs with every amino acid optimized to fold into the prescribed, stable structure. In this way they differ from natural proteins, whose folded structures represent a compromise between the competing requirements of optimum folding and biological function, leading to “frustrated” parts of the sequence that may be essential for function but are destabilizing to the fold. As evidence of their stability, the designed proteins melt at about 100 °C, Koga says, compared to 40–50 °C for a natural protein.
Koga and Tatsumi-Koga confess that marital competition fuels their work. So far, Tatsumi-Kota is winning. She designed three of the five proteins that appear in the paper, says Koga.
One might wonder how designing a new protein from scratch could be better than starting with natural proteins, given the head start that nature has in evolving effective functions and stable conformations. In fact, evolution has honed the structures of many proteins so precisely that it can be difficult to get the backbone to budge into another conformation to accommodate a new function, Baker says. “This paper provides the opportunity to design the structure and function at the same time,” says Baker. “Rather than taking an already existing scaffold, now you can design a backbone to order for exactly the function you want to carry out.” That will be the next step — incorporating function into the designs.


Naturedoi:10.1038/nature.2012.11767
发表于 2013-2-2 11:55:04 | 显示全部楼层
Google译者工具包准备好了= =
Proteins made to order
Researchers design proteins from scratch with predictable structures.
蛋白质结构设计
研究人员设计从头开始预测的蛋白结构。
Jessica Marshall
07 November 2012
2012年11月7号
Proteins are an enormous molecular achievement: chains of amino acids that fold spontaneously into a precise conformation, time after time, optimized by evolution for their particular function. Yet given the exponential number of contortions possible for any chain of amino acids, dictating a sequence that will fold into a predictable structure has been a daunting task.
蛋白质分子是一个巨大的成就:它一次又一次自发地折叠成一个精确的构象,被为了其特定的功能进化的氨基酸链优化。然而,由于任何氨基酸链可能形状极多,把一个确定的的序列折叠成一个可预测的结构一直是一项艰巨的任务。

图片说明:一种蛋白质的3维结构和其功能密切相关。(The 3-dimensional structure of a protein is intimately related to its function.)(来源:PASIEKA/SCIENCE PHOTO LIBRARY)
发表于 2013-2-2 11:58:33 | 显示全部楼层
Now researchers report that they can do just that. By following a set of rules described in a paper published in Nature today1, a team from David Baker’s laboratory at the University of Washington in Seattle has designed five proteins from scratch that fold reliably into predicted conformations. In a blind test, the team showed that the synthesized proteins closely match the predicted structures.
现在,研究人员报告说他们可以做到这一点。通过以下一组在《自然》发表的一篇论文中描述的规则,一支来自西雅图华盛顿大学的大卫·贝克的实验室的团队设计了五种可靠地从头开始预测蛋白质折叠构象的方法。在双盲试验中,研究小组发现,合成蛋白质密切与预测结构相匹配。
发表于 2013-2-2 12:03:41 | 显示全部楼层
“There’s really only one previous example of a protein that has been designed from scratch: that’s Top7 which we designed 10 years ago2,” said Baker, a computational structural biologist. “Top7 was sort of a one-off case,” he says. In the new work, the team presents a generalized approach.

“What you have now is a flexible set of building blocks for nanoscale assembly,” says Jeremy England, a molecular biophysicist at the Massachusetts Institute of Technology in Cambridge, who was not involved in the work.
“真的已经有从头就开始设计的一种蛋白质,例子中只有一个:那就是TOP7,来自于10年前生物学家计算的结构,”贝克说。“ TOP7是一个偶然的情况,”他说。在新的工作中,该小组提出了一个广义可用的方法。

“你现在得到的是纳米级装配的一套灵活的积木,”杰里米·英格兰,没有参与这项工作的麻省理工学院的分子生物物理学家在剑桥说。

点评

不好意思评分系统有点问题。。修复后再给你发拼图。。  发表于 2013-2-5 14:18

评分

参与人数 1基本分 +50 收起 理由
昂宿星团人 + 50 翻译辛苦!

查看全部评分

发表于 2013-2-5 14:54:52 | 显示全部楼层
本帖最后由 arthur200000 于 2013-2-6 10:02 编辑

回复LZ:分不用啦==
其实我用了Google译者工具包==偷懒啦~
====分割线=====
喂!哪儿有这样给拼图的!

点评

帖子改名了,别不认识了。。另外你还差一段,另外另外评分标准改了,剩下的不加分了哟 ̄▽ ̄  发表于 2013-2-17 19:41

评分

参与人数 1维基拼图 +50 收起 理由
昂宿星团人 + 50 这个算啥偷懒。。翻译出来好读就是好~~.

查看全部评分

发表于 2013-2-6 10:13:34 | 显示全部楼层
本帖最后由 arthur200000 于 2013-2-6 10:15 编辑

原文
Bending rules
The work was spearheaded by husband-and-wife team Nobuyasu Koga and Rie Tatsumi-Koga, protein engineers in Baker’s group. After observing the backbone structures of thousands of proteins, they developed some intuitive rules they wanted to test.
Protein strands typically form helices and other classic secondary structures that in turn fold into the final protein shape. The team realized that these structures could be made to twist in one direction or another depending on the length of the loops that connected them. By choosing the right sequence lengths between these building blocks, the team could predict which way they would fold.
Using these and additional criteria, the team developed a number of candidate sequences designed to fold into one of five structures. They vetted these sequences using the group’s Rosetta@home program, which uses volunteers’ home computer power to run protein-folding simulations. Rosetta volunteers test-folded each sequence hundreds of thousands of times. About 10% of the sequences had predicted structures that were stable and matched what the team intended. The winning sequences did not match any known natural proteins.
翻译
弯曲规则
这项工作被来自贝克的研究小组的夫妻蛋白质工程师信泰古贺和惠巽古河带领。在观察了成千上万的蛋白质主链结构之后,他们发现了他们想测试的一些直观的规则。
蛋白纤维形成螺旋和其他经典的二级结构,而折叠成最终的蛋白质的形状。团队意识到,这些结构可以在一个方向或另一个扭转,取决于连接他们的环的长度。通过在这些块之间选择正确的序列长度,团队可以预测他们将折叠的方式。
使用这些和其他标准,该小组研制出的候选序列折叠成一个五层结构。他们使用团队的Rosetta @ home的程序审查了这些序列,此BOINC程序使用志愿者的家用电脑的电力来运行蛋白质折叠模拟。Rosetta志愿者测试每个序列的折叠数千次。约10%的序列预测的结构是稳定的,并且能够匹配团队的想法。最后得到的序列不与任何已知的天然蛋白质序列符合。

 楼主| 发表于 2013-2-6 10:42:56 来自手机 | 显示全部楼层
arthur200000 发表于 2013-2-5 14:54:52
本帖最后由 arthur200000 于 2013-2-6 10:02 编辑

回复LZ:分不用啦==
其实我用了Google译者工具包==偷懒啦~
====分割线=====
喂!哪儿有这样

原文字数除5无误啊来自: Android客户端
发表于 2013-3-10 17:06:48 | 显示全部楼层
本帖最后由 arthur200000 于 2013-3-10 17:40 编辑

Platonic proteins
The team synthesized these proteins and sent them to Gaetano Montelione of Rutgers University in Piscataway, New Jersey, who determined the proteins’ structures by nuclear magnetic resonance (NMR) imaging without having seen the predicted structures. Then they compared the two versions. “It is remarkable how well the predicted structures agree with the high-quality NMR structures,” Montelione says.
Baker's proteins are in a sense “platonic ideals”, he says: simple backbone constructs with every amino acid optimized to fold into the prescribed, stable structure. In this way they differ from natural proteins, whose folded structures represent a compromise between the competing requirements of optimum folding and biological function, leading to “frustrated” parts of the sequence that may be essential for function but are destabilizing to the fold. As evidence of their stability, the designed proteins melt at about 100 °C, Koga says, compared to 40–50 °C for a natural protein.
Koga and Tatsumi-Koga confess that marital competition fuels their work. So far, Tatsumi-Kota is winning. She designed three of the five proteins that appear in the paper, says Koga.
One might wonder how designing a new protein from scratch could be better than starting with natural proteins, given the head start that nature has in evolving effective functions and stable conformations. In fact, evolution has honed the structures of many proteins so precisely that it can be difficult to get the backbone to budge into another conformation to accommodate a new function, Baker says. “This paper provides the opportunity to design the structure and function at the same time,” says Baker. “Rather than taking an already existing scaffold, now you can design a backbone to order for exactly the function you want to carry out.” That will be the next step — incorporating function into the designs.

翻译中。。。

柏拉图式“完美”的蛋白质
该研究小组合成了这些蛋白质,把他们送给新泽西州罗格斯大学(Rutgers University)的Gaetano Montelione,他使用核磁共振成像(NMR)、在没有看到预测结构的情况下查看结构。然后,他们比较了两个版本的结构。“这与核磁共振结果有着了不起的相似度,”Montelione说。
贝克的蛋白质是在一定意义上柏拉图式的理想”的,他说:简单的骨干和每一个为了符合规则、稳定而优化的氨基酸组成了这样的结构。在这种方式中,它们从天然蛋白质,其折叠结构是兼顾最佳的折叠和生物学功能的代表。但这导致了一些“令人沮丧”的序列,该序列可能有必不可少的功能,但却有着不稳定的折叠方式。作为它们的稳定性的证据,研究小组所设计的蛋白质在约100℃高温下融化,古河说,而相比天然蛋白质,其典型熔点仅40-50℃。
古贺和巽哥打京承认婚姻竞争(?)是他们研究的动力。到目前为止,巽哥打京即将胜利。她设计了五个中三个出现在论文的蛋白质,古贺说。
有人可能会问,为何要从头开始设计的蛋白质?他们认为自然蛋白质先发展,自然有不断发展的功能和稳定的构象。事实上,进化已经如此精确地定下了许多蛋白质​​的结构,从而它很难得到的骨干进化成另一种构象,以适应新的功能,Baker说。“本文设计的结构和功能,同时都为获得一个好蛋白提供了机会,”贝克说。“,与使用一个已经存在的支架相比,现在你可以设计一个骨干结构,它正有你想要的功能,可以量身定做。”这将是下一个步骤 —— 将功能融入设计中。
发表于 2013-3-10 17:43:03 | 显示全部楼层
完成了喵

点评

摸摸头喵  发表于 2013-3-11 22:27
这里竟然不给拼图了TAT  发表于 2013-3-10 17:43
发表于 2013-3-10 19:41:11 | 显示全部楼层
本帖最后由 YuezhouLyu 于 2013-4-10 18:38 编辑

机器翻译的简直无法直视。。。我来吐吐槽。。。吐到哪儿是哪儿,有时间还会继续吐。。。
ps: 这篇文章放托福阅读里很适合啊!某些长句改改放在SAT Writing里也挺好的。。。

吐槽开始:

Proteins made to order
定做蛋白质

Researchers design proteins from scratch with predictable structures.
研究人员根据可预测的结构从头设计制作蛋白质

Proteins are an enormous molecular achievement:
蛋白质是分子层面的巨大成就:

chains of amino acids that fold spontaneously into a precise conformation, time after time, optimized by evolution for their particular function.
肽链自发折叠出精巧的构象,为了进化出特殊机能而一次又一次被优化。

Yet given the exponential number of contortions possible for any chain of amino acids, dictating a sequence that will fold into a predictable structure has been a daunting task.
然而由于肽链折叠方式极多,把肽链折叠成一个可预测的结构一直是一项艰巨的任务。

Now researchers report that they can do just that.
现在,研究人员宣告这个可以实现啦。

By following a set of rules described in a paper published in Nature today1, a team from David Baker’s laboratory at the University of Washington in Seattle has designed five proteins from scratch that fold reliably into predicted conformations.
来自华盛顿大学西雅图(U of Washington - Seattle),大卫·贝克(David Baker)实验室的小组,根据今天出版的《自然》杂志中一篇阐述折叠规则的文章1,从头设计制作了5个蛋白,并可靠地折叠出了预测的构象。

In a blind test, the team showed that the synthesized proteins closely match the predicted structures.
小组在盲测中表明,合成出的蛋白与预测的结构相吻合。

"There’s really only one previous example of a protein that has been designed from scratch: that’s Top7 which we designed 10 years ago2,"said Baker, a computational structural biologist. "Top7 was sort of a one-off case," he says.
“以前,仅仅只有一个蛋白被从头设计制作出来,那就是10年前的Top7 2”计算结构生物学家贝克说,“Top7 只管一次用。”【红字部分有待商榷,请提出宝贵的意见~】

In the new work, the team presents a generalized approach.
在新的工作中,小组展示了一个一般化的方法。

"What you have now is a flexible set of building blocks for nanoscale assembly.” says Jeremy England, a molecular biophysicist at the Massachusetts Institute of Technology in Cambridge, who was not involved in the work.
“你现在有的一套可以在纳米尺度下搭的积木。”麻省理工学院(MIT)的分子生物学家杰里米·英格兰(Jeremy England)说。英格兰教授并没有参与此项工作。

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参与人数 2基本分 +6 维基拼图 +33 收起 理由
昂宿星团人 + 33 GJ喵,如果再有追加修改的话,在后面回复吧.
arthur200000 + 6 楼下你黑的。。。。。。算了你的分~\(≧▽.

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发表于 2013-3-11 09:01:48 来自手机 | 显示全部楼层
YuezhouLyu 发表于 2013-3-10 19:41:11
本帖最后由 YuezhouLyu 于 2013-3-10 19:43 编辑

机器翻译的简直无法直视。。。我来吐吐槽。。。吐到哪儿是哪儿,有时间还会继续吐。。。
ps: 这篇文章放托福阅读里很适

喵明明是人工修正过的……不要pia我><来自: Android客户端

点评

我还感叹机器什么时候能翻译这么好了= =如果对我吐槽有不明白的地方尽管问。。。。好歹我也是考过Sadistic Animal Test的人啦  发表于 2013-3-11 11:45
 楼主| 发表于 2013-4-7 16:23:07 | 显示全部楼层
YuezhouLyu 发表于 2013-3-10 19:41
机器翻译的简直无法直视。。。我来吐吐槽。。。吐到哪儿是哪儿,有时间还会继续吐。。。
ps: 这篇文章放托 ...

两点建议:
design,建议译为 设计制作 ,它是有这个解释的

倒数第三个槽点中:
one-off case 那里有点微妙,我的话会翻译成   top7只是某种罕见的巧合   ,不过貌似跟原文一比有点扭曲过头了。。求讨论。。
发表于 2013-4-10 18:31:57 | 显示全部楼层
昂宿星团人 发表于 2013-4-7 16:23
两点建议:
design,建议译为 设计制作 ,它是有这个解释的

第一点:完全同意。。。

第二点:感觉那个"one-off case"大概是“一次性事件”的意思。。。我读了一下也感觉“只管一次用”不太合适。。。这个翻译成“Top7仅仅是个例”怎么样?
的确很微妙呢><
 楼主| 发表于 2013-4-10 21:32:30 来自手机 | 显示全部楼层
YuezhouLyu 发表于 2013-4-10 18:31
第一点:完全同意。。。

第二点:感觉那个"one-off case"大概是“一次性事件”的意思。。。我读了一下也 ...

个例靠谱,大概查了下,top7是成功设计并合成过的,不是只成功合成过一次。
 楼主| 发表于 2013-4-21 15:26:15 来自手机 | 显示全部楼层
arthur200000 发表于 2013-2-6 10:13
原文
Bending rules
The work was spearheaded by husband-and-wife team Nobuyasu Koga and Rie Tatsumi-K ...

日本人夫妇的名字是古贺信康和古贺理绘
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