Human Proteonome Folding, Phase 2, рассчет структуры белков в человеческом теле Налаштування

[Rilian]

Human Proteome Folding Project
Phase 2

Официальные результаты проекта
Активные эксперименты
Human Microbiome Project - официальный сайт

http://homepages.nyu.edu/~rb133/wcg/thread_2010_03_10.html

Как присоединиться читайте в главном топике World Community Grid

Proteins are essential to living beings. Just about everything in the human body involves or is made out of proteins.

What are proteins?
Proteins are large molecules that are made of long chains of smaller molecules called amino acids. While there are only 20 different kinds of amino acids that make up all proteins, sometimes hundreds of them make up a single protein.

Adding to the complexity, proteins typically do not stay as long chains. As soon as the chain of amino acids is built, the chain folds and tangles up into a more compact and particular shape that lets it conduct specific and necessary functions within the human body.

Proteins fold because the different amino acids like to stick to each other following certain rules. Imagine that amino acids are pop-beads of 20 different colors. The pop-beads are sticky, but sticky in such a way that only certain combinations of colors can stick together. This makes the amino acid chains fold in a particular way that creates proteins that are useful to the human body. Human cells have mechanisms to help the proteins fold properly and, equally important, mechanisms to get rid of improperly folded proteins.

How do proteins relate to human genes?
The collection of all of the human genes is known as "the human genome." Depending on how the genes are counted, there are over 30,000 genes in the human genome. Each gene, which is a section of a long chain known as DNA, dictates how to build the chain of amino acids for one of the 30,000 proteins. In recent years, scientists were able to map the sequence for each human gene. This means that we now know the sequence of amino acids in all of the human proteins. Thus, the human genome is directly related to the "human proteome," the collection of all human proteins.

The protein mystery
While researchers have learned a great deal about the human proteome, the functions of most of the proteins remain a mystery. The genes do not reveal exactly how the proteins will fold into their final shape, which is critical because that determines what a protein can do and what other proteins it can connect to or interact with.

Proteins are like puzzle pieces. For example, muscle proteins connect to each other to form a muscle fiber. They join together in a specific manner because of their shape, as well as other factors relating to the shape.

Everything that goes on in cells and in the body is very specifically controlled by the shape of the proteins that do or do not let proteins interlock with other proteins. For example, the proteins of a virus or bacteria may have particular shapes that enable it to break through the cell membrane, allowing it to infect the cell.

The Human Proteome Folding Project
Знания структуры белков позволит ученым понять как белки выполняют свои биологические функции, а также как болезни блокируют белки от выполнения необходимых функций для поддержания здоровых клеток

The Human Proteome Folding Project will combine the power of millions of computers in a grid to help scientists understand how human proteins fold. The work to be done in this monumental task is shared across this grid, so that results can be achieved far sooner than would be possible with conventional supercomputers. With a greater understanding of protein structure, scientists can learn how diseases work and ultimately find cures for them.

When your grid agent is running, it is folding an amino acid chain in various ways and evaluating how well each folding follows the specific rules of how specific amino acids stick together or not. As computers try millions of ways to fold the chains, they attempt to fold the protein in the same way that it actually folds in the human body. The best shapes identified for each protein are returned to the scientists for further study.



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График проекта


Це повідомлення відредагував Rilian: Feb 4 2011, 00:23

[Kirilkaper]

World Community Grid Lecture Series - Human Proteome Folding project

Dear ******,

You are invited to participate in a live webcast on Octover 21, 2011 to hear an overview and update on World Community Grid's Human Proteome Folding project. The event will be hosted by Dr. Richard Bonneau from New York University.

Since 2006, World Community Grid has had the privilege of supporting the innovative research underway at New York University to use computers to predict the structure of proteins, the "molecular machines" of the human body. Knowing protein structure is a critical step in advancing the understanding of how proteins affect human health, providing scientists with the information they need to develop new cures for human diseases.

This is the "Human Proteome Folding - Phase 2" project that many of you run every day on your laptops and PCs for World Community Grid, helping us make progress towards aiding researchers in understanding how proteins perform their intended functions and also how diseases prevent proteins from maintaining healthy cells.

The webcast will take place on October 21, 2011, starting promptly at 11:00AM Eastern Daylight Time (USA), which is 15:00 Coordinated Universal Time. Please join a few minutes early so that you're sure not to miss anything.

Participants can listen to Dr. Bonneau while viewing an on-screen presentation. Time permitting, you will be able to ask Dr. Bonneau questions via a text chat interface.

Access to the webcast is via this link: https://apps.lotuslive.com/meetings/join?id=0327108

You can check if your computer is ready for the webcast at this link: https://www.conferenceservers.com/browser?b...=LLENGAGE_EN-US

And whether or not you can join the webcast, make sure your laptop, PC or Mac is running World Community Grid, and let your friends know this easy way to participate in helping humanity!

Also, please note that World Community Grid has added three new download servers to help support our additional growth. Download servers are used to send work to your computer. As a result of this change, your computer may prompt you to communicate with the IP addresses of these new servers. If you have experienced this, please click on this link for further information: http://www.worldcommunitygrid.org/forums/w...ad_thread,31492


Thank you,


The World Community Grid Team

P.S. After the webcast we will post the video of the webcast on YouTube, in the World Community Grid News & Update section, and we'll send you a link to the video.

[Rilian]

The Human Proteome Folding project research scientists have posted an informative status update on their web site. They highlight their recently published paper in Genome Research and an upcoming paper about the evolution of proteins. Future work is also discussed, including some work which should help the scientific community working on malaria.

You may review their update here.

World Community Grid Post - HPF2 Update, November 2011

Greetings to everyone,

It's been a stretch since the last update, but excitingly (!), we've been quite busy wrapping up ongoing projects with publications, and also getting our teeth into new projects and data. So, without further ado, I'd like to first mention our accepted and pending publications, and then go over the new data we're crunching and where it is leading us.

The lab has been very excited to recently have two gargantuan efforts come to fruition with the acceptance of one paper and the completion and submission of a second. The first, Kevin Drew (et al.)'s, is an enormous work covering nearly everything we do in terms of protein structure and function prediction, and was made conceivable in the first place and achievable in the second by support of World Community Grid computing cycles.

The paper will be available in the journal Genome Research this month (November 2011). The abstract is as follows, and the lab spent extra to ensure an open license so that the paper could be viewed in full - take a look!

The incompleteness of proteome structure and function annotation is a critical problem for biologists and, in particular, severely limits interpretation of high-throughput and next-generation experiments. We have developed a proteome annotation pipeline based on structure prediction, where function and structure annotations are generated using an integration of sequence comparison, fold recognition and grid-computing enabled de novo structure prediction. We predict protein domain boundaries and 3D structures for protein domains from 94 genomes (including Human, Arabidopsis, Rice, Mouse, Fly, Yeast, E. coli and Worm). De novo structure predictions were distributed on a grid of over 1.5 million CPUs worldwide (World Community Grid). We generate significant numbers of new confident fold annotations (9% of domains that are otherwise unannotated in these genomes). We demonstrate that predicted structures can be combined with annotations from the Gene Ontology database to predict new and more specific molecular functions.

The paper can be viewed here: http://genome.cshlp.org/content/early/2011...75.111.abstract

Also, take a quick look at this seminal image from the paper - predicting domain boundaries, and using the grid to do de Novo structure prediction for unknown domains:

The second piece of good news is that another paper involving protein structure folding has recently been submitted for publication.

Melissa Pentony et al. have presented work considering sites of positive selection (areas of faster-than-average evolution) in the proteomes of five major plant species in order to study plant protein evolution, and have extended this analysis in a novel way by mapping sites of positive selection in proteins onto 3D predicted protein structures. This is exciting as, seen in the image below, it allows scientists to visualize where sites of increased evolution occur structurally on a protein.

[Image: a DNA-binding protein interacting with DNA, with positively selected residues of protein highlighted by blue spheres. Notice, then, that the parts of the protein interacting with DNA are under selected evolution!]

This work is currently being revised, and will be available for preview shortly - Another example of the grid producing data (predicted protein structure!) that can be used in diverse biological studies to extend analyses and relate biological phenomena to the fundamental molecular machines of the human body (proteins!).

Now on to what's been grinding on your CPUs...

Processing for the Human Microbiome Project (described in the last update) was finished with batch 'ok', and from there we moved on to Plasmodium Yoelii Yoelii, which made up batches 'ol' through 'op'.

I mentioned the bacteria Plasmodium Yoelii Yoelii in the previous status update and very briefly in my last forum post. Pyy is a rodent malaria used a model organism for studying malaria in general, and specifically human malaria (the concept of using very similar model organisms is common in the field, and is extremely helpful for increasing data set size and inferring properties of an organism from known properties in a model). For this reason, having accurate structural knowledge of Pyy is important for the malaria research community.

Knowing this, we looked up our collaborator Jane Carlton, recently moved to the NYU Department of Biology, and asked for the most up-to-date data. We were pointed to a resource called PlasmoDB ( http://plasmodb.org/plasmo/ ), and from the data we found there put together five batches of novel protein domains to be sent for de Novo structure prediction.

After malaria...

After malaria, while we updated our post-processing analyses to make better use of grid results, we moved on to Archaea, which make up the third domain of life (the other two being bacteria and eukaryotes). Archaea are incredibly interesting and important organisms - they're now getting a lot of press due to their role in the function of the human colonic system, and interestingly, some species are known to thrive in incredibly harsh environments, such as salt lakes and hot springs.

For more information on Archaea, check this Berkeley resource or, of course, wikipedia - Archaea. The archaea Haloferax and Haloarcula comprise batches oq through ow.

Pausing the Archaeas

At the moment, we have a large list of archaea to analyze, but have switched priorities due to some extremely exciting new ideas regarding protein function prediction based on machine learning techniques (which sounds AI-cool, but is more statistics-cool) which we have developed in house, and on revised proteome data for Mouse and Human.

We have decided to re-run this new mouse and human data through our domain prediction pipeline and send results to the grid in order to get the best possible protein structure data. With improvements and updates to our pre- and post-processing methods and increased sampling on the grid (we're now folding 100,000 structures per domain, up from 30,000!), we will be able to approach the problem of protein structure prediction in a novel and potentially game-changing way with the best data available.

In terms of work batches, ox through ql (we skipped the letter p in batch naming) are made up of Mouse protein data, with ox through ql running on the grid now. After ql, new Human data will take over.

The first culmination of this mouse and human redo, along with our new protein function prediction ideas, will be our presence at a nation-wide protein structure/function jamboree hosted by the University of California, San Diego in early December, where we will present the work of the grid and its incorporation into our new methods to hopefully astounding effect!

Cross your fingers for us…

[vitalidze1]

в мене пендінг валідейшн по цьому проекту вже днів 5 тягнеться, щось вони довго не проходять перевірку...

[Rilian]

Resizing of HPF2 work units

For future work units, we have decreased the average run time from 9 hours to 6 hours for this project. This will allow users with slower computers or computers which are available less time to have a better chance of completing work units for this project. It will take about 20 days for the existing longer work units to be sent out, so the new shorter work units won't be seen until after this time.

Seippel
Apr 13, 2012

с этого момента все задания будут считаться в среднем 6 часов

[Rilian]

Опубликовали работу "The Plant Proteome Folding Project: Structure and Positive Selection in Plant Protein Families" в журнале Genome Biology and Evolution

Researchers have published a paper in the journal Genome Biology and Evolution, which documents their findings studying a number of plant genomes, their proteomes, evolution and protein structure.

Lay Person Abstract:

Melissa Pentony et al. have presented work considering components of proteins exhibiting faster-than-average evolution in the proteomes of five major plant species, including rice (Oryza sativa) and Arabidopsis thaliana (an important model organism for plant study). They describe new information on the relationship between evolution and protein structure in plants.

The World Community Grid has contributed to this study by providing a much more structurally complete view of unknown and understudied proteins from five plant families than was previously available. The results from the Human Proteome Folding project produced 29,202 protein structures contributing to this project, of which 4,764 were very high-confidence. This should eventually assist agricultural scientists to better understand important plant and food crops, how to breed them for disease resistance, better nutrition and to better handle environmental stress.

Technical Abstract:

Despite its importance, relatively little is known about the relationship between the structure, function, and evolution of proteins, particularly in land plant species. We have developed a database with predicted protein domains for five plant proteomes (http://pfp.bio.nyu.edu/) and used both protein structural fold recognition and de novo Rosetta-based protein structure prediction to predict protein structure for Arabidopsis and rice proteins. Based on sequence similarity, we have identified ~15,000 orthologous/paralogous protein family clusters among these species and used codon-based models to predict positive selection in protein evolution within 175 of these sequence clusters. Our results show that codons that display positive selection appear to be less frequent in helical and strand regions and are overrepresented in amino acid residues that are associated with a change in protein secondary structure. Like in other organisms, disordered protein regions also appear to have more selected sites. Structural information provides new functional insights into specific plant proteins and allows us to map positively selected amino acid sites onto protein structures and view these sites in a structural and functional context.

Access to Paper:

To view the paper, please click here .

[Rilian]

Апдейт статуса проекта!

http://bonneaulab.bio.nyu.edu/wcg/thread_2012_07_01.html

[Rilian]

Paper published in the journal Molecular Cell using Human Proteome Folding project results

http://www.worldcommunitygrid.org/about_us...o?articleId=204

Summary
A paper was published in the journal Molecular Cell, which used results from the Human Proteome Folding project in identifying proteins which regulate processes in human cells.

Paper Title:

“The mRNA-Bound Proteome and its Global Occupancy Profile on Protein-Coding Transcripts”

Lay Person Abstract:

The Bonneau lab at NYU collaborated with Markus Landthaler and colleagues from the Max Delbruch Center for Molecular Medicine, Berlin, contributing in an effort to discover and study novel RNA-binding proteins in the human proteome. These proteins play an important role in regulating activity in the cell. Some of the proteins have been implicated in diseases such as Alzheimer’s, muscular diseases, cancers and others. This information should help scientists in further understanding of disease processes, possibly leading to better treatments.

The Landthaler group at the MDC put together a landmark experiment for discovering RNA-binding proteins - a type of protein extremely important to human genetic systems. They then contacted the Bonneau lab for computational analysis. World Community Grid has provided predicted structures for a more complete structural landscape, contributing greatly to the analysis of human protein structure and function. This analysis allowed the Bonneau lab to verify experiment results from the Landthaler lab, lending confidence to their methods and providing data on RNA-binding proteins found via experimental methods. Furthermore, cutting-edge function prediction methods were developed and proved in this experiment, which will feature World Community Grid data in future publications.

Technical Abstract:

Protein-RNA interactions are fundamental to core biological processes, such as mRNA splicing, localization, degradation, and translation. We developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics and to display the protein occupancy on mRNA transcripts by next-generation sequencing. Application to a human embryonic kidney cell line identified close to 800 proteins. To our knowledge, nearly one-third were not previously annotated as RNA binding, and about 15% were not predictable by computational methods to interact with RNA. Protein occupancy profiling provides a transcriptome-wide catalog of potential cis-regulatory regions on mammalian mRNAs and showed that large stretches in 3′ UTRs can be contacted by the mRNA-bound proteome, with numerous putative binding sites in regions harboring disease-associated nucleotide polymorphisms. Our observations indicate the presence of a large number of mRNA binders with diverse molecular functions participating in combinatorial posttranscriptional gene-expression networks.

Access to Paper:

To view the paper, please click here.

[Bel]

Среднее время выполнения всех заданий увеличилось на 15%!

[Rilian]

Новости проекта

World Community Grid Post - HPF2 Update, June/July 2012
http://bonneaulab.bio.nyu.edu/wcg/thread_2012_07_01.html

World Community Grid Post - HPF2 Update, Fall/Winter 2012
http://bonneaulab.bio.nyu.edu/wcg/thread_2012_12_04.html

[Sonechko]

Блін...



Тепер навіть незнаю що кранчити, все вже на сапфірах...

[KING100N]

Проект внезапно подошел к концу - The first project to run on World Community Grid, the Human Proteome Folding project, is coming to a close.. Судя по данным с этой таблички, осталось 24 дня счета. Рекомендую всем, желающим получить очередной баджик налегать на проект после завершения пентатлона. Например, себе )

Summary
The first project to run on World Community Grid, the Human Proteome Folding project, is coming to a close. They have added greatly to the knowledge of protein structures, providing their results to other scientists via their data base resources.



The first project to run on World Community Grid, the Human Proteome Folding project, is coming to a close.

They have greatly added to the knowledge of protein structures, providing their results to other scientists via their data base resources. In addition, the project has published many high quality peer reviewed papers. These publications and the data base resources have helped many other scientists with their own work to understand disease processes and to accelerate their search for cures.

We are a little sad to see the project ending in a few weeks, but we are also very proud of this project's accomplishments. Please read their latest project update for more details.

We thank you, our member volunteers, for contributing to this project and we hope you will continue to contribute to our other projects, as well as the many new ones we expect to launch before too long.

[Rilian]

Вау круто!

Наверное выпустят третью фазу с новыми алгоритмами Rosetta@home

[Rilian]

Взято отсюда http://bonneaulab.bio.nyu.edu/wcg/thread_2013_05_16.html

There are some exciting research possibilities he and others are considering such as investigating how mutations alter protein structure. Perhaps one of these ideas may grow into a new World Community Grid project at some time in the future.

[Rilian]

Осталось 21 день до завершения проекта!

Предлагаю подключить его всем у кого он не подключен, и ускорить это событие!

[Rilian]

Задания будут выдаваться еще 1 неделю! Запасайте кэш если вы охотитесь за бейджиком