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发表于 2006-1-10 12:34:49
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http://boinc.equn.com/rosetta/rah_about.htm
What is Rosetta@home?
Why predict and design protein structures and complexes?
How accurate are our predictions?
Plans for the future
Feedback to participants
View Windows Media videos of Rosetta predictions
什么是 Rosetta@home?
为什么要进行蛋白质及聚合物的结构预测和设计?
我们的预测精度?
长远计划
反馈用户
观看 Rosetta 的预测过程视频(WMV格式)
What is Rosetta@home?
什么是 Rosetta@home?
Rosetta@home is a scientific research project that uses internet-connected computers to predict and design protein structures, and protein-protein and protein-ligand interactions. Our goal is to develop methods that accurately predict and design protein structures and complexes, an endeavor that may ultimately help researchers develop cures for human diseases (See the Human Proteome Folding Project, a collaborative effort to apply our software on the human genome). Our project relies on individuals, like you, who donate time on their computers to collectively provide the computing power necessary to further develop, test, and improve our methods.
Rosetta@home 是一项利用联网的计算机来预测和设计蛋白质结构及蛋白质之间或蛋白质与配体间相互作用的研究项目。我们的目的是要寻找准确预测和设计蛋白质结构及聚合物的方法,这项工作将有助于研究人员寻找对付一些重大的人类疾病的途径(请查看人类蛋白质折叠研究计划,它使用我们的软件来对人类基因进行研究)。我们的项目依赖于每一个像你一样愿意贡献出电脑空闲时间的志愿者。你们提供的计算力将使我们有能力来发展、测试和改善我们的方法。
The Rosetta@home project uses a software package called Rosetta, which was initially developed for predicting the three-dimensional structure of a protein from it's amino acid sequence. Over the years, Rosetta has evolved to also include protein design and the prediction of protein complexes. At the core of Rosetta are the physical model of macromolecular interactions and algorithms for finding the lowest energy structure for an amino acid sequence (protein structure prediction) or a protein-protein complex (protein docking) and for finding the lowest energy amino acid sequence for a protein structure or protein-protein complex (protein design). We hope to continually improve the physical model and the search algorithms based on feedback from prediction and design tests carried out by the Rosetta@home project.
Rosetta@home 项目使用名为 Rosetta 的软件包,Rosetta 最早是用来通过蛋白质的氨基酸序列来预测其结构。经过多年的发展,Rosetta 已经具备了蛋白质设计及蛋白质聚合物预测的能力。Rosetta 的核心部分包括大分子相互作用的物理模型和寻找氨基酸序列或蛋白质聚合物的最低能量结构(蛋白质结构预测)的算法以及寻找特定蛋白质或聚合物结构的最低能量氨基酸序列(蛋白质设计)。我们希望通过 Rosetta@home 项目所进行的预测和设计测试而进一步改善软件的物理模型及搜寻算法。
In order to do this, we need your help. We believe that we are getting closer to accurately predicting and designing proteins and protein complexes, one of the holy grails of computational biology. But in order to prove this, we require an enormous amount of computing resources, an amount that can only be provided by the world's largest super computers ....or volunteers like you. Like the well known SETI@home project, Rosetta@home will enable us to conduct our research using donated time on computers connected to the internet. Please join us in our efforts!
为了达到这个目的,我们需要你们的帮助。我们相信我们已经离精确地预测和设计蛋白质或聚合物这一计算生物学领域中的圣杯已经相当近。但为了做到这一点,我们需要大量的计算资源,可以是世界上最大的超级计算机...或者是像你们一样的志愿者。就像知名的 SETI@home 项目,Rosetta@home 使得我们可以使用互联网上大量计算机的空闲时间来进行我们的研究。请加入到我们中来!
For more information, click on the following links:
A welcome from David Baker
Research Overview
David Baker Profile - Protein Folding (UW Cyberscience Symposium Article)
Science News
Back to top ^
更多详细信息,可以查看下面的链接:
来自 David Baker 的欢迎信
研究概况
David Baker 档案 - 蛋白质折叠 (发表于华盛顿大学的Cyberscience Symposium)
科学新闻
回到页面顶部 ^
Why predict and design protein structures and complexes?
为什么要进行蛋白质及聚合物的结构预测和设计?
Proteins are the molecular machines and building blocks of life. Their functions and interactions are critical for the chemical and biological framework and processes of all living organisms. The function of a protein and how it iteracts with other molecules are largely determined by it's shape (the three-dimensional structure). Proteins are initially synthesized as long chains of amino acids and, for the most part, they cannot function properly until they fold into intricate globular structures. Understanding and predicting the rules that govern this complex folding process -- involving the folding of the main backbone and the packing of the molecular side chains of the amino acids -- is one of the central problems of biology. Knowing how proteins fold and interact with other molecules and determining their functions may ultimately lead to drug discoveries and cures for human diseases. Currently, millions of dollars are being spent in structural genomics efforts to determine the structures of proteins experimentally using X-ray crystallography and nuclear magnetic resonance (NMR). If this could be done computationally, it would significantly reduce the cost and revolutionize structural biology. Designing protein structures and complexes also offers significant scientific and practical benefits. If one can design completely new structures, one can potentially design novel molecular machines -- proteins for carrying out new functions as therapeutics, catalysts, etc. And finally, there's the evolutionary question of whether the folds that are sampled in nature are the limit to what's possible; or whether there are quite different folds that are also possible. Understanding the rules that govern folding and design may help answer this question.
蛋白质是生命的基础构造,其功能和相互间的作用对于所有生物体的化学及生物结构和作用至关重要。蛋白质的功能和它与其它分子的相互作用很大程序是由其形状(即三维结构)所决定的。蛋白质合成时只是一长串的氨基酸,然后只有在它折叠成某种错综复杂的球状结构后才能真正起作用。了解和预测主宰这一复杂折叠过程的规则(包括主体的折叠以及旁链的填充)是当今生物学的核心问题之一。了解蛋白质的折叠和与其它分子的相互作用以及它的功能将可能有利于找到对付人类疾病的药物或治疗方法。目前实验中用X射线或核磁共振方法来得到蛋白质的结构需要耗费大量的资金。如果可以通过计算来解决,将可以大量减少结构生物学研究的费用。蛋白质及聚合物的结构设计也有相当大的理论和现实意义。只要能设计出全新的结构,就可能设计出新奇的分子机器 - 具备治疗、催化等方面功能的蛋白质。最后一个问题是自然界中是否已经包含了所有可能的折叠?或许还有一些完全不同的折叠也是可能的?理解主宰蛋白质折叠和设计的规则将有助于这个问题的解答。
Please visit the following Wikipedia links for more general information about:
Proteins
Protein folding
Protein structure prediction
Protein design
Back to top ^
请点击下面的维基链接及获取更多的信息:
蛋白质
蛋白质折叠
蛋白质结构预测
蛋白质设计
回到页面顶部 ^
How accurate are our predictions?
我们的预测精度?
Rosetta was shown repeatedly to be one of the best methods for predicting the three-dimensional structures of proteins in the Critical Assessment of Techniques for Protein Structure Prediction (CASP), and has also been successful in CAPRI, the Critical Assessment of Prediction of Interactions. A highlight of CASP6 was the first de novo blind prediction that used our high-resolution refinement methodology to achieve close to high-resolution accuracy. The relatively short sequence (76 residues) allowed us to apply our all-atom refinement methodology not only to the native sequence but also to the sequence of many homologs. The center of the lowest energy cluster of structures turned out to be remarkably close to the native structure (1.5 ?). The-high resolution refinement protocol decreased the RMSD from 2.2 ? to 1.5 ?, and the side chains pack in a somewhat native-like manner in the protein core. In CAPRI, predictors are given the structures of two proteins known to form a complex, and challenged to predict the structure of the complex. Our predictions for targets without significant backbone conformational changes were striking. Not only were the rigid-body orientations of the two partners predicted nearly perfectly but also almost all the interface side chains were modeled very accurately. Our design methods also have shown to produce accurate results. Particularly exciting recently is the creation of novel proteins with arbitrarily chosen three-dimensional structures. For example, our methods were used to design a 93-residue protein called TOP7 with a novel sequence and topology. TOP7 was found to be monomeric and folded, and the x-ray crystal structure of TOP7 is strikingly similar (RMSD of 1.2 ?) to the design model.
Rosetta 已在蛋白质结构预测关键技术分析大赛(CASP)上多次被证明是最好的蛋白质三维结构预测方法之一,在蛋白质相互作用预测关键技术分析大赛(CAPRI)中也表现不错。第六届 CASP 的亮点之一就是使用我们的高分辨率提炼方法进行的初次盲测取得了相当不错的结果。相对短的序列(包含76个基)允许我们不仅对自然序列,同时也对许多同系物使用了全原子提炼方法。结构的最低能量簇中心和实际的结构相当接近(1.5埃)。高精度提炼方法将RMSD从2.2埃降低到了1.5埃。蛋白质核心处的旁链填充也是以类似于自然界的方式进行的。在CAPRI大赛上,给定两个已知会聚合的蛋白质结构,要示预测出聚合物的结构。我们预测出的聚合物的主干部分准确度相当高!不仅主干的朝向预测几乎完美,接口处的旁链也都相当精确。近期更让人激动的是可任意选择三维结构的全新蛋白质的设计。我们的方法已经用于对名为TOP7的包含93个基的蛋白质的全新的次序及结构设计。TOP7 was found to be monomeric and folded,用X射线看到的TOP7的晶格结构与设计模型相当接近(RMSD为1.2埃)。
Plans for the future
长远计划
Our methods will be tested in upcoming CASP and CAPRI experiments and implemented in our publicly available protein structure prediction server, Robetta, which is currently used by hundreds of academic scientists from around the world for free, and has been shown to be one of the best fully-automated structure prediction servers in recent CASP experiments. If there are enough Rosetta@home participants, we also plan to use Rosetta@home to provide computational resources that will reduce the long wait period for structure predictions on the Robetta server and will enable us to add more functionality, such as design and docking, that we currently cannot provide because of limited computing resources. By integrating Robetta and Rosetta@home, volunteers, like you, will not only help our efforts, but will directly help the efforts of scientists from around the world doing critical research on biomedical issues such as cancer, SARS, HIV/AIDS, malaria, and much more.
我们的方法将在即将到来的 CASP 和 CAPRI 实验中进行检验,同时也将应用在我们的公共蛋白质结构预测服务器(Robetta)上。Robetta 当前正在被全世界数以千计的科学家们免费使用,并且已被近期的 CASP 实验证明为最好的结构预测服务器之一。如果 Rosetta@home 有足够多的参与者,我们计划使用 Rosetta@home 来提供计算资源,以减少 Robetta 服务器的压力,我们也将加入诸如设计和接合等目前由于计算能力有限而无法实现的功能。通过将 Robetta 和 Rosetta@home 集成在一起,像你一样的志愿者将不仅可以帮助我们,还可以直接帮助世界各地的科学家们进行生物医学方面的重要研究,比如癌症、SARS、爱滋、疟疾等等。
Feedback to participants
反馈用户
Wouldn't you, as a participant, like to know the results of the predictions made on your computer -- how accurate your best model was, how did it compare with others, what did it look like, who and how has it helped? We plan to provide such information on the Rosetta@home website and, when possible, link it to the predictions requested by scientists through the Robetta server. You can already keep track of the amount of computing work ("credits") that you have donated and compare it to others from our statistics page. Back to top ^
作为参与者的你难道不想知道在你的计算机上完成的预测结果吗?你完成的最佳模型的精度如何?和其他参与者比较呢?它看上去是怎样的?它是否帮助到了谁?我们计划在 Rosetta@home 的网站上提供类似的信息,可能的话,还将其关联到科学家提交的预测请求上。你现在已经可以知道你完成的任务量(积分)并且可以在我们的统计页面上与其他的参与者进行比较。
回到页面顶部 ^
View the following Windows Media videos of Rosetta:
观看 Rosetta 的预测过程视频(WMV格式)
folding Ubiquitin (file size 4M),
re-packing side-chains of TOP7 (file size 2.4M),
and selecting optimal side-chain rotamers for TOP7 (design) (file size 4.7M).
Note: Windows Media Player is required. Videos were created by Jens Meiler.
注意:播放上列视频需要安装媒体播放器。视频由 Jens Meiler 创建。
[ Last edited by Youth on 2006-2-16 at 15:53 ] |
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