Версія даної теми для друку

Автор: KoDAk May 9 2008, 17:29

Проект "Discovering Dengue Drugs – Together - Phase 1"

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http://www.worldcommunitygrid.org/projects_showcase/dddt/viewDddtMain.do

http://www.worldcommunitygrid.org/team/viewTeamInfo.do?teamId=J8H4J4QPN1
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Дата основания команды - Дата Капитан - Капитан
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http://distributed.org.ua/forum/index.php?showtopic=890


О проекте:
Старт -- Август 2007 / Статус-- активный
Поиск лекарств и вакцин от тропической лихорадки, энцефалита Западного Нила, гепатита С и желтой лихорадки. Как только посредством компьютерного анализа будет уточнен состав вакцин, начнутся лабораторные и клинические испытания этих лекарств для определения их эффективности.

Mission
The mission of Discovering Dengue Drugs – Together is to identify promising drug leads to combat the related dengue, hepatitis C, West Nile, and Yellow fever viruses. The extensive computing power of World Community Grid will be used to complete the structure-based drug discovery calculations required to identify these leads.

Significance
This project will discover promising drug leads that stop the replication of viruses within the Flaviviridae family. Members of this family, including dengue, hepatitis C, West Nile, and Yellow fever viruses, pose significant health threats throughout the developed and developing world. More than 40% of the world's population is at risk for infection by dengue virus. Annually, 1.5 million people are treated for dengue fever and dengue hemorrhagic fever. Hepatitis C virus has infected ~2% of the world's population. Yellow fever and West Nile viruses have also had significant global impact. Unfortunately, there are no drugs that effectively treat these diseases. Consequently, the supportive care necessary to treat these infections and minimize mortality severely strains already burdened health facilities throughout the world. The discovery of both broad–spectrum and specific antiviral drugs is expected to significantly improve global health.

Approach
One promising approach to combat these viruses and prevent them from causing disease is to develop drugs that inhibit the viral NS3 protease. The NS3 protease is an enzyme critical for virus replication, and its amino acid sequence and atomic structure are very similar among the different disease–causing flaviviruses. Since the atomic structure of the NS3 protease is known, we can utilize advanced structure–based computational drug discovery methods to identify small molecule protease inhibitors.

Dr. Stan Watowich and his research team at The University of Texas Medical Branch (Galveston, Texas, USA) have made significant progress in this direction, having discovered compounds that inhibit dengue and West Nile virus proteases and prevent virus replication in cell culture. However, additional drug candidates need to be discovered to improve the likelihood of converting drug leads into approved drugs for treating flavivirus infections.

Автор: Rilian May 19 2008, 09:00

Я подключился

Автор: Rilian Oct 25 2008, 17:01

С 12го октября в проекте не выдаются новые задания. Если вы хотитче чтобы компьютеры в это время не простаивали, а делали полезную работу, зайдите на страницу Мои Проекты (https://secure.worldcommunitygrid.org/ms/viewMyProjects.do) и поставьте галочку "If there is no work available for my computer for the projects I have selected above, please send me work from another project." - таким образом будут присылаться задания с других проектов WCG.

Причина приостановки проекта: университет University of Texas Medical Branch который проводит исследования, серьезно пострадал от урагана IKE. Если вы владеете английским, прочитайте подробности тут: http://www.chron.com/disp/story.mpl/editorial/6052627.html

Форум проекта на официальном сайте: https://secure.worldcommunitygrid.org/forums/wcg/listthreads?forum=261

Уже статистика разделена. Это видно как на глобальной статистике ( http://www.worldcommunitygrid.org/stat/viewProjects.do ), так и в профилях юзеров ( http://www.worldcommunitygrid.org/ms/viewMyMemberPage.do )

Автор: Rilian Dec 20 2008, 05:05

Hello from UTMB! No, we are not inactive. Yes, we are bringing this project back online. Yes, it is taking us longer than expected since we continually run into unexpected personnel and infrastructure surprises. But, behind the scenes, we are working hard and are committed to bringing this project back online. The coding and testing of Phase 2 (free energy calculations) of this project is occurring even as Phase 1 sits apparently silent.

Our main LINUX cluster used for pre/post processing of workunits and storage of the vast amount of information generated by your crunching computers was offline. Now, only our 12 TB IBM DS3200 storage system is offline. We are reinstalling 3rd party interface boards and drivers to bring this system up (if this fails, we will move this storage system to another cluster, and work from there). Surprising as it may seem, this is taking time.

Thank you for your continued patience.

Best wishes to all for this Holiday Season from the DDD-T group at UTMB.

Stan Watowich

Автор: Rilian Jan 4 2009, 20:20

Через неделю обещают запуск проекта! Прогревайте процессоры!

Автор: Rilian Jan 18 2009, 22:35

Проект снова работает!

Автор: Rilian Jan 19 2009, 08:13

На core2duo 2,5Ghz задание выполняется около 5 часов.

Избыточность рассчетов - 1 ВЮ

Автор: gow Jan 19 2009, 08:52

а дедлайн каков?

Автор: Rilian Jan 19 2009, 09:55

14 дней.

То есть 1-гигагерцовый комп будет укладываться в дедлайн с запасом

Автор: Rilian Jan 19 2009, 18:37

On January 18, 2009, our World Community Grid project ”Discovering Dengue Drugs-Together” resumed sending out workunits to grid clients around the world. This project has been off-line since September 13, 2008, when Hurricane Ike devastated Galveston, Texas and our university. We thank World Community Grid members for their support and patience as we rebuild our damaged infrastructure and community. Much is left to do to fully recover, but at least this project is restored.

Our initial projections as to how long it would take to restart operations were clearly overly optimistic. Recounting the myriad of large and mundane problems that were faced to get back on-line is a little mind-numbing at this point. However, in brief, most personnel on this project lost their homes and possessions, and needed to focus on family recovery. Our main computer cluster sustained damage and remains unstable (contrary to initial assessments). Disk storage components were lost to flood waters and have taken time to replace. Institutional support for this project was reduced as the University of Texas Medical Branch cut ~25% of its staff.

On the positive side, this project is now running better than ever before. We have moved our main computational tasks (those required to prepare workunits for World Community Grid and analyze results returned from the grid) to the supercomputers housed at the Texas Advanced Computer Center (TACC; www.tacc.utexas.edu) in Austin, Texas. Our pre- and post-processing calculations execute 10x faster in this environment compared to our in-house 30-node computer cluster. Thus, we have established a nice synergy between one of the world’s most powerful supercomputers and the world’s largest computer grid. Our storage capabilities have increased in (1) size with the local addition of IBM’s 12 TByte DS3200 disk subsystem and (2) robustness with redundant storage occurring at TACC and locally. Programs required to accurately calculate free energy of binding (Phase 2 of this project) have been tested and optimized at TACC, and are being ported to the grid. Thus, the computational side of this project is more powerful and dynamic than before Hurricane Ike.

The current tasks before us are clear. (1) We will resume pre-clinical characterization of potential dengue, West Nile, and hepatitis C virus protease inhibitors predicted by our Phase 1 calculations. Several Phase 1 compounds have shown promising in vitro activity. (2) Launch Phase 2 free energy of binding calculations to reduce the large false-positive rates associated with virtual screening. Finally, our newly established synergistic World Community Grid/TACC environment will help us tackle additional global health projects – with IBM’s support we are about to launch a collaborative drug discovery effort with researchers in South America to target the Leishmania parasite.

As stated before, we greatly appreciate the computer time that has been unselfishly provided by the members of the World Community Grid. Your interest and support has made this grid one of the most powerful computing resources on the planet!

All my best,
Stan

18 января 2009, наши всемирного сообщества сетку проекта "Discovering Dengue Drugs-Together" возобновил отправку workunits к сетке клиентов по всему миру. Этот проект был офф-лайн с 13 сентября, 2008 году, когда ураган "Айк разрушенной Galveston, штат Техас, и наш университет. Мы благодарны мировому сообществу сетку члены за их поддержку и терпение, пока мы не восстановим нашу разрушенной инфраструктуры и в обществе. Многое остается сделать, чтобы полностью восстановиться, но по крайней мере, этот проект будет восстановлен.

Наши первоначальные прогнозы в отношении того, как долго он будет принимать для возобновления операции были явно чересчур оптимистичными. Пересчет множества больших и прозаический проблем, с которыми сталкиваются вернуться на линию немного ума-numbing на этом точку. Тем не менее, в кратце, большинство персонала на этот проект потерял свои дома и имущество, а также должна быть направлена на восстановление семьи. Наш главный компьютер кластера повреждение, и по-прежнему нестабильно (в отличие от первоначальных оценок). Диск хранения компонентов были потеряны для паводковых вод, и имели время для замены. Институциональная поддержка этого проекта была сокращена, как Техасский университет Медицинское отделение вырежьте ~ 25% ее сотрудников.

С позитивной стороны, этот проект в настоящее время работает лучше, чем когда-либо прежде. Мы переехали наши основные вычислительные задачи (которые требуются для подготовки workunits для мирового сообщества сетку и анализировать результаты вернулись из сетки) для суперкомпьютеров размещены в Техасе Расширенный Компьютер Центр (TACC; www.tacc.utexas.edu) в Остине, штат Техас . Наши пред-и пост-обработки расчетов 10x быстрее выполнить в этой среде по сравнению с нашими в дом 30-узла кластера. Таким образом, мы наладили хорошее взаимодействие между одной из самых мощных суперкомпьютеров и крупнейшая в мире компьютерная сеть. Наши возможности хранения увеличилось в (1) размером с местными добавлением 12 IBM DS3200 Тбайт дисковой подсистемы и (2) с избыточной надежности хранения, происходящие на TACC и на местном уровне. Программы необходимы для точного расчета свободной энергии связывания (фаза 2 проекта), были проверены и оптимизированы на TACC, и в настоящее время перенесен на сетке. Таким образом, вычислительные стороне данного проекта является более мощным и динамичным, чем до урагана Айк.

В настоящее время перед нами задачи ясны. (1) Мы возобновим до клинических характеристик потенциальных денге, Западного Нила, и вируса гепатита С ингибиторы протеазы предсказал нашим расчетам Этап 1. Несколько Этап 1 соединений показали многообещающие в VITRO деятельности. (2) Этап 2 Ракета свободной энергии обязательных расчетов по сокращению большого ложного-положительных ставок, связанных с виртуальными скрининга. Наконец, наша недавно созданного Всемирного синергического сообщества сетку / TACC среды поможет нам решить дополнительных глобальных проектов в области здравоохранения - при поддержке IBM, мы собираемся приступить к осуществлению совместного обнаружения наркотиков совместно с исследователями в Южной Америке к целевой Leishmania паразита.

Как отмечалось ранее, мы высоко ценим время, чтобы компьютер был бескорыстно представленной членами мирового сообщества сетку. Ваш интерес и поддержку добился этой сетке один из самых мощных вычислительных ресурсов на планете!

С лучшими пожеланиями,
Стэн

Автор: Death Jan 19 2009, 22:02

как Техасский университет Медицинское отделение вырежьте ~ 25% ее сотрудников

Автор: Rilian Jan 22 2009, 08:58

получил серебрянную медальку

Автор: Rilian Jan 26 2009, 15:41

Получил золотую медаль за 90 дней рассчетов

Автор: nikelong Feb 13 2009, 17:22

http://www.boinc-af.org/content/view/743/219/

Автор: nikelong Feb 14 2009, 19:49

http://www.dp.by/wiki/Projects/Discoveringdenguedrugs

Автор: Rilian May 25 2009, 11:15

Hello again from Galveston! Below is a status update that will be posted on our web site update board. However, I thought I would get it out via the forums as well.

Thanks again for all your help!

We are back on track with our DiscoveringDengueDrugs-Together project, and life is returning to some semblance of normalcy in Galveston and at UTMB. We thank World Community Grid members for their support and patience during the past 6 months following Hurricane Ike.

The Autodock phase (Phase 1) of our dengue project is now complete! We have screened (i.e., computationally tested) more than 3 million potential drug candidates against each of 10 different proteases from dengue, West Nile, and hepatitis C viruses. Inhibiting these target proteases prevents virus replication. We continue to analyze the 30 million Phase 1 results. We are using biochemical, cell-based, and small animal assays to characterize some of the inhibitors identified during our recently completed Phase 1 calculations.

The CHARMM phase (Phase 2) of our project is being optimized at Texas Advanced Computer Center (TACC; www.tacc.utexas.edu) in Austin, Texas and ported by IBM to the grid for testing. This phase will perform extensive molecular dynamics calculations to accurately calculate binding free energies for the best potential drug candidates predicted in Phase 1. These calculations will significantly reduce the number of false positive predictions produced in Phase 1, thereby increasing our success rate for identifying experimentally active compounds from ~10% to >80%. Launch of Phase 2 is anticipated for early summer, 2009.

As we prepare to launch Phase 2 of our project to discover drugs for dengue, West Nile, and hepatitis C infections, we will also begin Autodock calculations in support of a collaborative drug discovery effort against leishmaniasis disease. This work is done in partnership with researchers from Universidad de Antioquia, Colombia (http://www.pecet-colombia.org). Leishmania affects ~12 million people throughout the tropics, subtropics, and southern Europe, with ~2 million new cases each year. The disease is spread by the bite of sand flies infected the Leishmania parasite. Although a handful of antimicrobials exist to treat some forms of leishmaniasis, concerns about their modes of delivery, effectiveness, resistance, and cost spur our drug discovery efforts into novel anti-Leishmania drugs. For this project, scientists in Colombia identified a set of enzymes critical for survival of the Leishmania parasite. Atomic structures exist for each of these enzymes, this allowing us to computationally examine our drug candidate library for compounds that prevent the Leishmania enzymes from functioning.

As reported earlier, this project is now running better than ever before. We have moved our main computational tasks (those required to prepare workunits for World Community Grid and analyze results returned from the grid) to the supercomputers housed at TACC. This establishes a nice synergy between one of the world’s most powerful supercomputers and the world’s largest computer grid. Our storage capabilities have increased in size and robustness with redundant storage occurring at TACC and locally on our 12 TByte IBM DS3200 disk system.

As stated before, we greatly appreciate the computer time that has been unselfishly provided by the members of the World Community Grid!

- Stan

Автор: cosmo_vk May 26 2009, 09:45

нипонял, этот как это фаза 1 закончена! У меня до сих пор задания висят в обработке, а по их словам 2 фаза еще только передана для тестирования в IBM.

да и по вчерашним сливам в 45 тысяч не особо это смахивает на "законченность".

Автор: Tamagoch Aug 4 2009, 09:22

на сайте WCG в разделе проектов написано:

что это значит? я уже не получу медальку? или можно попедалить?

Автор: Rilian Aug 4 2009, 10:00

ВЮ в текущей фазе проекта закончились

Автор: Rilian Aug 23 2009, 14:29

Первая фаза проекта завершена 11 августа 2009

Автор: Rilian Oct 31 2009, 21:29

Discovering Dengue Drugs – Together (Phase 1) Completion

World Community Grid is pleased to announce that as a result of the immense contribution of computing power from our members, Phase 1 of the Discovering Dengue Drugs – Together project finished on August 11, 2009.

The project launched on August 21, 2007 and ran for nearly 2 years. During that time over 159,000 members processed more than 25,500,000 results which required nearly 12,000 years of computing power from about 400,000 computers.

The project was interrupted for 17 weeks when Hurricane Ike made landfall in Galveston, Texas, USA, on September 17, 2008 and significantly damaged the research facility. Fortunately, none of the members of the research team and their families were injured and the facility was put back in working order. The project was re-started in late January, 2009.

A part of this project end, we also made some website updates. On the Research Pages and in the forums, the project is moved from Active Research to Completed Research.

Completing this project is a significant contribution to the research of Dengue Fever, Hepatitis C, West Nile, Yellow Fever and other diseases caused by the Flaviviridea family of viruses. This same research would have taken 205 years to complete on the computers that the researchers from UTMB had available to them in 2007.

Phase 1 was designed to serve as a comprehensive screening of approximately 3 million small "drug-like" molecules and identify several thousand molecules which attach to these virus enzymes in a manner that disables them. Molecules such as these may lead to drugs which can keep the disease from spreading in the body. The purpose of Phase 1 was to reduce the number of molecules being examined to only those that are the most promising candidates. These molecules will be further examined in Phase 2.

Phase 2 of the project will run each of the molecules identified in phase 1 through computationally demanding free energy calculations. The molecules that make it through this screening will be the candidates that show the most promising interactions with the virus enzymes and will be taken forward and further examined in the laboratory.

At this time, the researchers are busy performing post-processing on the results from Phase 1 and preparing for Phase 2. You may read about these plans and get the latest update from Dr. Stan Watowich in the following forum thread: http://www.worldcommunitygrid.org/forums/wcg/viewthread?thread=26616.

On behalf of the Discovering Dengue Drugs - Together research staff at the University of Texas Medical Branch in Galveston, Texas, USA, we wish to express our thanks to you for contributing your computer power to this project. With your contribution, this phase of the project was completed in a fraction of the time it would otherwise have taken.

Автор: Rilian Dec 12 2009, 02:39

Видео

http://www.msnbc.msn.com/id/21134540/vp/34370816