Experiment 41 involves screening the Enamine library of 2.345 million compounds against the two allosteric sites on the surface of HIV protease. This experiment is similar to Exp. 36, but a different, much larger library of compounds is being screened, and some new targets are being included. The first part of this experiment involves docking compounds against the two allosteric-fragment-bound crystal structures presented in our recent article in Chemical Biology and Drug Design, vol. 75: 257-268 (March 2010). Three other, brand new crystal structures from Dave Stout's lab that involve allosteric fragments bound to these two sites on the surface of HIV protease are also being used as targets. Two of these new targets are presented in a new research manuscript from the Stout lab that is currently being peer-reviewed. When this paper is accepted, we will describe these targets in more detail and provide a link to this new paper.
This is by far the largest experiment we have submitted to FightAIDS@Home; it involves faah33,529 - faah45,253.
The results of these calculations started arriving at TSRI on 5/15/2012.
Rilian
Dec 4 2012, 00:03
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 36,852
Days Left - 529
End Date - May 15, 2014
также, видео от ученых проекта
Webcast and Question & Answer session replay - featuring Lead World Community Grid Scientist Viktors Berstis and Dr. Alex Perryman:
This webcast commemorated World AIDS Day 2012 and gave World Community Grid members an opportunity to hear about the cutting-edge research being done with the FightAIDS@Home project. During the webcast, Dr. Perryman outlined the exciting discoveries that he and other members of Dr. Art Olson’s computational research lab have recently made in collaboration with other research teams at Scripps and around the world. They have run simulations that identified several chemical compounds that can “dock” with allosteric sites on the HIV protease molecule and may help to inhibit its function. These compounds could form the basis of therapeutic drugs to combat HIV “superbug” strains, and at the very least they suggest compelling new avenues for further research.
And the FightAIDS@Home research will continue, thanks to the World Community Grid volunteers. The computing power supplied by the members is absolutely critical to support this research and enable these advances in HIV treatment.
As always, thank you for your support of World Community Grid research projects and please stay tuned for future webcasts!
Rilian
Dec 16 2012, 19:06
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 36,970
Days Left - 510
End Date - May 3, 2014
Rilian
Dec 16 2012, 20:34
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 37,095
Days Left - 497
End Date - April 27, 2014
Rilian
Dec 24 2012, 09:47
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 37,223
Days Left - 477
End Date - April 14, 2014
Rilian
Dec 31 2012, 01:06
December 30, 2012 update
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 37,351
Days Left - 457
End Date - April 1, 2014
Project Completion - 32.61 %
Rilian
Jan 7 2013, 12:25
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 37,483
Days Left - 443
End Date - March 25, 2014
Project Completion - 33.73 %
Rilian
Jan 13 2013, 18:09
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 37,613
Days Left - 429
End Date - March 18, 2014
Experiment 41 Completion - 34.84 %
Rilian
Jan 20 2013, 22:43
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 37,750
Days Left - 416
End Date - March 12, 2014
Experiment 41 Completion - 36.01 %
Rilian
Jan 28 2013, 01:03
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 37,879
Days Left - 402
End Date - March 5, 2014 Experiment Completion - 37.11 %
Rilian
Feb 3 2013, 21:10
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 37,998
Days Left - 395
End Date - March 5, 2014
Experiment Completion - 38.12 %
Rilian
Feb 8 2013, 12:17
Hi Everybody,
I just posted Volume 11 of the FightAIDS@Home Newsletter to:
This volume contains some of the same material that I presented in the last World AIDS Day Webinar , but I included more details and background information in the Newsletter.
Thank you all very much for your interest and your continued support, Alex L. Perryman, Ph.D.
Rilian
Feb 9 2013, 14:28
QUOTE
Although I have processed and measured the results for Experiments 31 to 40, I have not yet had a chance to filter them and visually inspect the top-ranked compounds. After discovering these promising hits in Experiment 30, I've been focusing on hit-to-lead development (that is, trying to use the structures of these hits to guide the process of making larger, more potent compounds). I've also been spending a lot of time on the GO Fight Against Malaria project: preparing targets, performing and analyzing positive control studies, submitting experiments, and processing their results. I've also visually inspected and ordered new candidate compounds against two different classes of targets from the GO Fight Against Malaria project: PfSUB1 and InhA from Mycobacterium tuberculosis (which is very similar to ENR from malaria). I only need to prepare a few more classes of targets against malaria, and then I'll have more time to devote to analyzing the results of the other FightAIDS@Home experiments.
I will visually inspect and order compounds from FightAIDS@Home experiments 31 to 40, but it will take time.
Thank you very much for your interest and your support, Alex L. Perryman, Ph.D.
QUOTE
Hi branjo,
Thank you very much!
I just wish the faculty search committees appreciated my unconventional, ambitious strategies half as much as you all. In the past couple years, I've applied for around 150 different Assistant Professor positions at universities throughout the U.S. (and a few in Canada and Europe, and one in Taiwan). But I've had no luck yet. If I can get a faculty position, then I'll be able to seamlessly continue and extend this research for many more years, and I'll be able to bring more personnel and other resources on board, as well. Please wish me luck on this front, too. It's still a tough job market for almost everyone, and that includes me.
Best wishes, Alex L. Perryman, Ph.D.
Rilian
Feb 15 2013, 16:45
В 2012 году в Украине от СПИДа умерли почти четыре тысячи человек
20 или 21 февраля 2013 на 10 часов приостановится выдача заданий проекта всвязи с обновлением версии AutoDock
QUOTE
Temporary stoppage of the FAAH project (February 20th or 21st) In order to switch FAAH to the new version of the science application (AutoDock), the FAAH project will temporarily be stopped. Since the switch needs to occur at a particular batch number, the exact time the outage will start can only be estimated. The current estimate is that the outage will happen on February 20th or 21st (this estimate will continue to be updated as the date approaches). The length of the outage is estimated to be less than 10 hours.
Seippel
Rilian
Feb 17 2013, 19:23
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 38,150
Days Left - 429
End Date - April 22, 2014
Experiment Completion - 39.42 %
Rilian
Feb 24 2013, 18:55
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 38,260
Days Left - 431
End Date - April 1, 2014
Experiment Completion - 40.36 %
Rilian
Mar 3 2013, 19:12
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 38,362
Days Left - 439
End Date - April 16, 2014
Experiment Completion - 41.23 %
Rilian
Mar 4 2013, 09:07
Ученые в США сообщают, что им, судя по всему, удалось вылечить маленькую девочку, рожденную с вирусом ВИЧ,
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 38,440
Days Left - 461
End Date - June 14, 2014
Experiment Completion - 41.90 %
Rilian
Mar 17 2013, 15:45
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 38,571
Days Left - 456
End Date - June 16, 2014
Experiment Completion - 43.02%
Rilian
Mar 26 2013, 00:10
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 38,713
Days Left - 439
End Date - June 6, 2014
Experiment Completion - 44.23 %
*** Above update is based on information from 3/24/2013 ***
Rilian
Mar 31 2013, 21:45
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 38,844
Days Left - 424
End Date - May 29, 2014
Experiment Completion - 45.35 %
Rilian
Apr 9 2013, 20:31
Украина - один из лидеров по количеству больных ВИЧ-СПИД в Европе, но большинство людей с ВИЧ не имеет доступа к лекарственным препаратам, которые позволили бы им вести нормальную жизнь.
Experiment 41 involves screening the Enamine library of 2.345 million compounds against the two allosteric sites on the surface of HIV protease. This experiment is similar to Exp. 36, but a different, much larger library of compounds is being screened, and some new targets are being included. The first part of this experiment involves docking compounds against the two allosteric-fragment-bound crystal structures presented in our recent article in Chemical Biology and Drug Design, vol. 75: 257-268 (March 2010). Three other, brand new crystal structures from Dave Stout's lab that involve allosteric fragments bound to these two sites on the surface of HIV protease are also being used as targets. Two of these new targets are presented in a new research manuscript from the Stout lab that is currently being peer-reviewed. When this paper is accepted, we will describe these targets in more detail and provide a link to this new paper.
Alien может меня поправить, но как я понял, Alex Perryman, главный ученый FAAH и GFAM, открыл новый способ рассчитывать ингибиторы к белкам, используя только опеределенную часть белка. То есть с помощью рентгеновской кристаллографии они определяют 3Д структуру части белка, оцифровывают ее, и используют докинг, перебирая все возможные синтетические белки, чтобы проверить их влияние на исходный белок, участвующий в образовании определенных болезней (ВИЧ, малярия).
Я зашел на их сайт, и у этой лаборатории за 5 месяцев этого года (2013) уже сделано 9 публикаций!
Вобщем, можно сказать что FAAH находится на самом передовом фронте биоинформатических исследований, и очень важно их поддерживать в данный момент!
Rilian
May 26 2013, 19:14
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 40,247
Projected Days Left - 200
Projected End Date - December 12, 2013
Experiment Completion - 57.32%
Alien
May 26 2013, 19:46
QUOTE(Rilian @ May 25 2013, 10:53)
Alien может меня поправить, но как я понял, Alex Perryman, главный ученый FAAH и GFAM, открыл новый способ рассчитывать ингибиторы к белкам, используя только опеределенную часть белка. То есть с помощью рентгеновской кристаллографии они определяют 3Д структуру части белка, оцифровывают ее, и используют докинг, перебирая все возможные синтетические белки, чтобы проверить их влияние на исходный белок, участвующий в образовании определенных болезней (ВИЧ, малярия).
Я не вчитывался, но там идея должна быть такой. Получаем координаты белка, а если его какой-то части нет - домоделировать. Далее оптимизировать структуру, а потом если известен активный сайт подбирать к нему лиганды. Судя по всему, они ищут несколько сайтов на белке, что интересно. Вижу в его статье 2011 года они используют МД, что есть правильно, т.к. структура полученная после кристаллизации не есть конформационно нативной, в отличии от полученной методом ЯМР.
То есть, результаты полученные после докинга на часть кристалла не есть информативными и являются малоперспективными без дальнейшего изучения комплекса методам МД. Они могут иметь малую корреляцию с экспериментом, а успешность подбора может и не достигать 0.1 %. Подобранный успешный лиганд может еще негативно влиять на один из остальных 99.99% белков из-за чего он не будет внедрен в практику лечения.
Вывод: необходимо обращать внимание на работы, которые используют современные подходы к изучению проблемы. Это комбинированные методы докинг->МД->ММ\КМ. Докинг на статическую структуру да и еще рентген мало что даст на практике.
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 40,665
Projected Days Left - 156
Projected End Date - November 11, 2013
Experiment Completion - 60.88%
Rilian
Jun 13 2013, 23:19
Новая информация о проекте
We also started collaborating with many other prominent experts on HIV, as part of a newly-created Center called the "HIVE". See: http://fightaidsathome.scripps.edu/ and http://hive.scripps.edu/ . In fact, we will soon expand the FightAIDS@Home project and start targeting three different allosteric sites on HIV reverse transcriptase that were recently discovered and three different allosteric sites of HIV integrase that were also recently discovered. In addition, we will soon add the ability to perform docking calculations with the software "AutoDock Vina" on FightAIDS@Home, which will enable us to increase the speed and scale of our virtual screens against these three drug targets from HIV/AIDS by several orders of magnitude.
Вкратце, создан новый центр по изучению ВИЧ
А также, проект будет проводить эксперименты на 6 недавно открытых точках ВИЧ
Мы на самом остром краю исследований!
Rilian
Jun 17 2013, 13:15
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 41041
Projected Days Left - 128
Projected End Date - October 22, 2013
Experiment Completion - 64.09%
Projected WU remaining approximately 19,300,000
Rilian
Jun 23 2013, 18:22
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 41504
Projected Days Left - 99
Projected End Date - September 29, 2013
Experiment Completion - 68.04%
осталось ВЮ із єксперімента 41: 17,150,000
Rilian
Jul 2 2013, 09:42
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 41994
Projected Days Left - 76
Projected End Date - September 13, 2013
Experiment Completion - 72.22%
Projected WU remaining approximately 14,892,000
At the present rate we are chewing through about 4% of the experiment 41 per week.
Rilian
Jul 8 2013, 12:24
WEEKLY UPDATE - based on work averaged over the last 8 weeks:
Current Batch - 42428
Projected Days Left - 61
Projected End Date - September 06, 2013
Experiment Completion - 75.92%
Projected WU remaining approximately 12,947,000
The pace is still accelerating with over 2,000,000 WU in the last seven days.
--
Интересно, какой будет новый эксперимент?
Rilian
Jul 10 2013, 10:17
график завершения эксперимента 41
когда синяя линия пересечется с зеленой, эксперимент завершен