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  • richardmitnick 10:16 pm on July 21, 2014 Permalink | Reply
    Tags: , , , FightAIDs@home, , ,   

    From WCG: “Pioneering a Molecular Approach to Fighting AIDS” 

    World Community Grid

    Dr. Arthur Olson
    Professor, The Scripps Research Institute
    21 Jul 2014

    Summary
    World Community Grid is being featured at the 20th International AIDS Conference which begins today in Melbourne, Australia. Dr. Arthur Olson, FightAIDS@Home principal investigator, shares his perspective on how World Community Grid is helping his team develop therapies and a potential cure for AIDS.

    The Scripps Research Institute’s FightAIDS@Home initiative is a large-scale computational research project whose goal is to use our knowledge of the molecular biology of the AIDS virus HIV to help defeat the AIDS epidemic. We rely on World Community Grid to provide massive computational power donated by people around the world to speed our research. The “virtual supercomputer” of World Community Grid enables us to model the known atomic structures of HIV molecules to help us design new drugs that could disrupt the function of these molecules. World Community Grid is an essential tool in our quest to understand and subvert the HIV virus’s ability to infect, spread and develop resistance to drug therapies.

    FightAidsOlsonLab@home

    Since the early 1980s – when AIDS was first recognized as a new epidemic and a serious threat to human health – our ability to combat the HIV virus has evolved. Using what we call “structure-based drug discovery,” researchers have been able to use information about HIV’s molecular component to design drugs to defeat it. Critical to this process has been our ability to develop and deploy advanced computational models to help us predict how certain chemical compounds could affect the HIV virus. The development of our AutoDock modelling application – combined with the computational power of World Community Grid – represents a significant breakthrough in our ability to fight HIV.

    By the mid 1990s, the first structure-based HIV protease inhibitors were approved for the treatment of AIDS. These inhibitors enabled the development of highly active antiretroviral therapy (HAART), which in turn resulted in a rapid decline of AIDS deaths where such treatment was available. In the intervening years, thanks in part to the U.S. National Institute of General Medical Sciences AIDS-related Structural Biology Program, we have learned a lot about the molecular structure of HIV. But the more we understand the structure of the virus, the more complex our computational models need to be to unlock the secrets of HIV.

    World Community Grid has enabled our research to progress well beyond what we could have dreamed of when we started our HIV research in the early 1990s. Through our FightAIDS@Home project, we can screen millions of chemical compounds to evaluate their effectiveness against HIV target proteins – including those known to be drug-resistant. By deploying these and other methods, we have significantly increased our understanding of HIV and its ability to evolve to resist treatment. Using these computational capabilities, we have just begun working with an HIV Cure researcher to help us move beyond treatment in search of a cure.

    See the full article here.

    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”

    WCG projects run on BOINC software from UC Berkeley.

    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BETCHA!!

    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-

    Say No to Schistosoma

    GO Fight Against Malaria

    Drug Search for Leishmaniasis

    Computing for Clean Water

    The Clean Energy Project

    Discovering Dengue Drugs – Together

    Help Cure Muscular Dystrophy

    Help Fight Childhood Cancer

    Help Conquer Cancer

    Human Proteome Folding

    FightAIDS@Home

    Computing for Sustainable Water

    Mapping Cancer Markers
    Mapping Cancer Markers Banner

    World Community Grid is a social initiative of IBM Corporation
    IBM Corporation
    ibm

    IBM – Smarter Planet
    sp


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  • richardmitnick 3:22 pm on July 16, 2014 Permalink | Reply
    Tags: , , , FightAIDs@home, ,   

    From FAAH@home: “Improved efficiency and processing capabilities for FightAIDS@Home” 

    FAAH
    FightAIDS@home

    16 Jul 2014
    The FightAIDS@Home research team

    Summary
    New methods and processes help the research team process World Community Grid data more efficiently and provide more accurate docking techniques.

    As the volume of data generated by World Community Grid volunteers for our FightAIDS@Home (FAAH) project has increased, so has our need to optimize how we handle and store that data. In this project update, we discuss new improvements in how we process the extremely high result data rate you generate, which is allowing us to focus more resources toward the analysis of FAAH data. Further, improved docking techniques are being created and applied from the results of deeper analysis coupled with ongoing experimental data from our collaborators.

    model
    Example of repositioned side-chain, histidine, by Vina cycling through the original space-filling representation, original stick representation (orange), and new position compared to old position (dotted black lines).

    Processing your results faster

    Managing the very large data throughput generated by World Community Grid volunteers for FAAH is a great challenge. Beside the scientific results we have achieved over the years, we also have developed novel software and protocols to process, analyze and store the results you generate quickly and efficiently.

    Recently, we exploited the parallel computational resources available at Scripps. In the last few months, we have shifted our processing of the incoming World Community Grid data to our local High Performance Computing cluster, Garibaldi. Since the implementation of the AutoDock Vina software for FAAH last year, you have generated several terabytes of compressed docking results each month, which was putting a strain on our storage system. Until recently, most of our work and resources have been focused on processing this data to make it suitable for deeper analysis. We had to devote most of our local computational power to this processing. With our new methods, we have increased the processing rate by several orders of magnitude with the use of multiple processors and the optimization of processing scripts. Processing a batch that used to take between 30 minutes to few hours now takes just a few minutes. Streamlined scripts and parallel processing has yielded 180,000 processed batches in two weeks.

    We have created new analysis programs using structural and statistical methods to mine more information from the results you generate. Statistical analysis tools will first be used to reduce over 5 million docked compounds to a few thousand top-ranking candidates. Structural information will then be used to cull the list further by filtering for key intermolecular interactions and against unfavorable interactions. A new database structure that will incorporate these programs is being developed to handle this large and fast-growing flood of results. Once optimized, the whole processing and analysis workflow will be fully automated.

    Importantly, what we have learned and are learning from these refined methods to handle big data will be made available in the AutoDockTools suite, which is utilized by many research labs worldwide.

    Improved protein-ligand binding modeling capabilities

    Proteins are typically large molecules and often can bend or flex in various ways at various points and at normal temperatures they rapidly bend to many or all of the possible configurations (bent shapes). When searching for ligands that might attach to a protein target, the ligand might not match the shape of the protein in one of its configurations, but might match in another configuration of the protein. By considering more configurations of the protein, it is more likely that a ligand can be found which matches one of the protein’s configurations. Since February 2014, we have been running flexible receptor side-chain Vina jobs on FAAH, which we expect to enhance our docking results. While our typical docking methods hold the protein structure rigid, the flexibility feature in AutoDock Vina allows selected residue side chain conformations to be sampled along with the flexible ligand molecule. This enables the protein pocket to adopt alternate shapes to better model protein-ligand binding and the so-called “induced fit”, minimizing the bias of using a rigid target structure. Currently, we are testing this approach on several sites (LEFGF, FBP, and Y3) in HIV integrase.

    The downside of performing flexible receptor calculations is that the search complexity increases, and computing run-times are therefore 5 to 10 times longer. The World Community Grid staff has been adjusting their methods to account for the different Flexible Vina work unit. Once these dockings have finished and the analyses performed, we will be able to optimize our application of Flexible Vina on World Community Grid and extend it to other targets.

    Another way to minimize rigid-protein bias in traditional docking is to dock to an ensemble of protein structures. Two ways to generate these ensembles, both used in FAAH dockings, are molecular dynamics (MD) simulations and simply using multiple available structures for a given protein receptor. The last hundred experiments have included ensembles ranging from tens to sometimes hundreds of receptor structures. Ensembles add another layer of analysis with the goal of achieving a more accurate ranking of compounds from several sources of data.

    Further experimentation

    Despite the encouraging results on the first hits previously reported, we are encountering experimental issues that are making the process of identifying hits very challenging. As often happens in science (and particularly in HIV-related experiments!), it is hard to achieve robust and consistent statistics from biological assays.

    See the full article here.

    FightAIDS@Home is a project run by the Olson Laboratory that uses distributed computing to contribute your computer’s idle resources to accelerate research into new drug therapies for HIV, the virus that causes AIDS. FightAIDS@Home made history in September 2000 when it became the first biomedical Internet-based grid computing project. FightAIDS@Home was started with Scott Kurowski, founder of Entropia. People all around the World continue to donate their home computer’s idle cycles to running our AutoDock software on HIV-1 protease inhibitor docking problems. With the generous assistance of IBM, we joined World Community Grid in late 2005, and launched FightAIDS@Home on World Community Grid on 21 November, 2005.

    How do I join the FightAIDS@Home Project?

    All you need to do is download and install the free client software. Once you have done this, your computer is then automatically put to work and you can continue using your computer as usual.

    Faah Screensaver


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  • richardmitnick 12:26 pm on July 14, 2014 Permalink | Reply
    Tags: , , FightAIDs@home, , ,   

    FROM WCG: “Better tools for AIDS drug research” 

    FAAH
    FightAIDS@home

    FightAIDS@Home is a project run by the Olson Laboratory that uses distributed computing to contribute your computer’s idle resources to accelerate research into new drug therapies for HIV, the virus that causes AIDS. FightAIDS@Home made history in September 2000 when it became the first biomedical Internet-based grid computing project. FightAIDS@Home was started with Scott Kurowski, founder of Entropia. People all around the World continue to donate their home computer’s idle cycles to running our AutoDock software on HIV-1 protease inhibitor docking problems. With the generous assistance of IBM, we joined World Community Grid in late 2005, and launched FightAIDS@Home on World Community Grid on 21 November, 2005.

    How do I join the FightAIDS@Home Project?

    All you need to do is download and install the free client software. Once you have done this, your computer is then automatically put to work and you can continue using your computer as usual.


    ScienceSprings is powered by MAINGEAR computers

    24 Jun 2014

    Summary
    The Scripps research team published a paper proving the effectiveness of a method to more accurately predict bindings between protein targets and drug candidates, which could benefit FightAIDS@Home and other World Community Grid drug discovery projects.

    Paper Title:

    “Virtual screening with AutoDock Vina and the common pharmacophore engine of a low diversity library of fragments and hits against the three allosteric sites of HIV integrase: participation in the SAMPL4 protein–ligand binding challenge”

    Lay Person Abstract:

    The Olson Lab at The Scripps Institute collaborated to participate in the “SAMPL4 Challenge” which evaluated methods to predict protein target to drug candidate bindings. Olson’s lab in cooperation with Levy’s lab at Rutgers University were able to prove the utility of a method to reduce false positives and therefore potentially reduce the amount of laboratory work required to validate computational results. This should ultimately be a benefit to research projects such as FightAIDS@Home and other drug search projects on World Community Grid.

    A link to the paper is here.
    See the full article here.

    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”

    WCG projects run on BOINC software from UC Berkeley.

    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BETCHA!!

    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-

    Say No to Schistosoma
    sch

    GO Fight Against Malaria
    mal

    Drug Search for Leishmaniasis
    lish

    Computing for Clean Water
    c4cw

    The Clean Energy Project
    cep2

    Discovering Dengue Drugs – Together
    dengue

    Help Cure Muscular Dystrophy
    md

    Help Fight Childhood Cancer
    hccf

    Help Conquer Cancer
    hcc

    Human Proteome Folding
    hpf

    FightAIDS@Home
    faah

    Computing for Sustainable Water

    Computing for Sustainable Water

    World Community Grid is a social initiative of IBM Corporation
    IBM Corporation
    ibm

    IBM – Smarter Planet
    sp


    ScienceSprings is powered by MAINGEAR computers

     
  • richardmitnick 7:58 pm on July 13, 2014 Permalink | Reply
    Tags: , , FightAIDs@home, ,   

    From FightAIDS@home: 

    FAAH
    FightAIDS@home

    hive

    Happy new year! Since February 2014, some FightAIDS@Home experiments have been using AutoDock Flexible Vina.

    vinahive
    Note: one AutoDock “batch” involves docking up to 1,000 compounds, while one AD Vina batch involves docking up to 10,000 compounds. Batches of Vina Experiments starting from Experiment 149 (from batch 865236) now include up to 100K compounds.

    FightAIDS@Home is a project run by the Olson Laboratory that uses distributed computing to contribute your computer’s idle resources to accelerate research into new drug therapies for HIV, the virus that causes AIDS. FightAIDS@Home made history in September 2000 when it became the first biomedical Internet-based grid computing project. FightAIDS@Home was started with Scott Kurowski, founder of Entropia. People all around the World continue to donate their home computer’s idle cycles to running our AutoDock software on HIV-1 protease inhibitor docking problems. With the generous assistance of IBM, we joined World Community Grid in late 2005, and launched FightAIDS@Home on World Community Grid on 21 November, 2005.

    How do I join the FightAIDS@Home Project?

    All you need to do is download and install the free client software. Once you have done this, your computer is then automatically put to work and you can continue using your computer as usual.


    ScienceSprings is powered by MAINGEAR computers

     
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