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  • richardmitnick 3:24 pm on April 24, 2017 Permalink | Reply
    Tags: Move to IBM Cloud, WCG   

    From WCG: “World Community Grid Moves to IBM Cloud” 

    New WCG Logo

    WCGLarge

    World Community Grid (WCG)

    24 Apr 2017

    Summary
    On May 15, World Community Grid will begin migrating to IBM Cloud, as part of an effort to modernize and enhance our infrastructure capabilities. Our system will be unavailable for approximately 48 hours while the migration takes place, but otherwise the move will not affect most volunteers.

    1
    We’re happy to announce that World Community Grid is moving to IBM Cloud. Through this migration, we are leveraging more scalable and powerful hosting capabilities, as well as IBM and open source automation tools that make our development and deployment processes more efficient. This allows us to identify, diagnose and address major technical issues more quickly. Most significantly, IBM Cloud’s global footprint of more than 50 data centers across 19 countries allows us to expand more easily and prepares us for years of growth.

    The migration will begin on May 15 and is expected to last approximately 48 hours, during which World Community Grid will be unavailable. This means that volunteers will not be able to access the website, fetch new research or return completed work during that time.

    No action is required by most volunteers, as our systems will resume sending and receiving research tasks once the migration is complete. However, for individuals or organizations who have restricted firewall rules, you may need to update those rules in order to continue contributing, by allowing connections to our new IP address (169.47.63.74).

    Anyone with questions about this migration can post in this forum thread. We appreciate everyone’s support during this migration, which will provide a modern hosting environment for volunteers and researchers for years to come.

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    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.
    BOINCLarge

    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.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    MyBOINC

    “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-

    FightAIDS@home Phase II

    FAAH Phase II
    OpenZika

    Rutgers Open Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    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

    faah-1-new-screen-saver

    faah-1-new

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

    IBM – Smarter Planet
    sp

     
  • richardmitnick 1:48 pm on April 10, 2017 Permalink | Reply
    Tags: , , , WCG   

    From OpenZika at WCG: “OpenZika Researchers Continue Calculations and Prepare for Next Stage” 

    New WCG Logo

    WCGLarge

    World Community Grid (WCG)

    By: The OpenZika research team
    21 Mar 2017

    Summary
    The OpenZika researchers are continuing to screen millions of chemical compounds as they look for potential treatments for the Zika virus. In this update, they report on the status of their calculations and their continuing work to spread the word about the project.

    Zika depiction. Image copyright John Liebler, www.ArtoftheCell.com

    Project Background

    While the Zika virus may not be getting the continuous press coverage that it received in 2015 and 2016, it is still a threat to the health of people across the globe. New infections continue to be reported in both South America and North America, and medical workers are just beginning to assess the effects of the virus on young children whose mothers were infected while pregnant.

    The search for effective treatments is crucial to stemming the tide of the virus. In addition to the OpenZika project, several other labs are doing cell-based screens with drugs already approved by the US Food and Drug Administration (FDA) agency, but few to none of the “hit” compounds that have been identified thus far are both potent enough against Zika virus and also safe for pregnant women.

    Also, there are a number of efforts underway to develop a vaccine against the Zika virus. However, vaccines do not help people who already have the infection. It will be several years before they are proven effective and safe, and before enough doses can be mass produced and distributed. And even after approved vaccines are available and distributed to the public, not all people will be vaccinated. Consequently, in the meantime and in the future, cures for Zika infections are needed.

    ZIKV NS3 helicase bound to RNA with the predicted binding modes of five approved drugs (from our second set of candidates) selected by virtual screening. These candidates are shown as surfaces with different shades of green. The identification of these candidates and the video were made by Dr. Alexander L. Perryman [see below].

    We began the analysis phase of the project by focusing on the results against the apo NS3 helicase crystal structure (apo means that the protein was not bound to anything else, such as a cofactor, inhibitor, or nucleic acid) to select our first set of candidates, which are currently being assayed by our collaborator at University of California San Diego, Dr. Jair L. Siqueira-Neto, using cell-based assays. The NS3 helicase is a component of the Zika virus that is required for it to replicate itself.

    In the second set of screening results that we recently examined, we used the new crystal structure of NS3 helicase bound to RNA as the target (see the images / animation above). Similar to the first set of candidates, we docked approximately 7,600 compounds in a composite library composed of the US Food and Drug Administration-approved drugs, the drugs approved in the European Union, and the US National Institutes of Health clinical collection library against the new RNA-bound structure of the helicase. Below are the results of this second screening:

    232 compounds passed the larger collection of different energetic and interaction-based docking filters, and their predicted binding modes were inspected and measured in detail.
    Of the compounds that were inspected in detail, 19 unique compounds passed this visual inspection stage of their docked modes.
    From the compounds that passed the visual inspection, 9 passed subsequent medicinal chemistry-based inspection and will be ordered soon.

    Status of the calculations

    In total, we have submitted 2.56 billion docking jobs, which involved the virtual screening of 6 million compounds versus 427 different target sites. We have already received approximately 1.9 billion of these results on our server. (There is some lag time between when the calculations are performed on your volunteered machines and when we get the results, since all of the results per “package” of approximately 10,000 different docking jobs need to be returned to World Community Grid, re-organized, and then compressed before sending them to our server.)

    Except for a few stragglers, we have received all of the results for our experiments that involve docking 6 million compounds versus the proteins NS1, NS3 helicase (both the RNA binding site and the ATP site), and NS5 (both the RNA polymerase and the methyltransferase domains). We are currently receiving the results from our most recent experiments against the NS2B / NS3 protease.

    A new stage of the project

    We just finished preparing and testing the docking input files that will be used for the second stage of this project. Instead of docking 6 million compounds, we will soon be able to start screening 30.2 million compounds against these targets. This new, massive library was originally obtained in a different type of format from the ZINC15 server. It represents almost all of “commercially available chemical space” (that is, almost all of the “small molecule” drug-like and hit-like compounds that can be purchased from reputable chemical vendors).

    The ZINC15 server provided these files as “multi-molecule mol2” files (that is, many different compounds were contained in each “mol2” formatted file). These files had to be re-formatted (we used the Raccoon program from Dr. Stefano Forli, who is part of the FightAIDS@Home team) by splitting them into individual mol2 files (1 compound per file) and then converting them into the “pdbqt” docking input format.

    We then ran a quick quality control test to make sure that the software used for the project, called AutoDock Vina, could properly use each pdbqt file as an input. Many compounds had to be rejected, because they had types of atoms that cause Vina to crash (such as silicon or boron), and we obviously don’t want to waste the computer time that you donate by submitting calculations that will crash.

    By splitting, reformatting, and testing hundreds of thousands of compounds per day, day after day, after approximately six months this massive new library of compounds is ready to be used in our OpenZika calculations. Without the tremendous resources that World Community Grid volunteers provide for this project, we would not even dream of trying to dock over 30 million compounds against many different targets from the Zika virus. Thank you all very much!!!

    For more information about these experiments, please visit our website.

    Our PLoS Neglected Tropical Diseases paper, OpenZika: An IBM World Community Grid Project to Accelerate Zika Virus Drug Discovery, was published on October 20, and it has already been viewed over 4,000 times. Anyone can access and read this paper for free. Another research paper Illustrating and homology modeling the proteins of the Zika virus has been accepted by F1000Research and viewed > 3800 times.

    A group from Brazil, coordinated by Prof. Glaucius Oliva, has contacted us because of our PLoS Neglected Tropical Diseases paper to discuss a new collaboration to test the selected candidate compounds directly on enzymatic assays with the NS5 protein of Zika virus. They have solved two high-resolution crystal structures of ZIKV NS5, which have been recently released on the PDB (Protein Data Bank) (PDB ID: 5TIT and 5U04).

    Our paper entitled “Molecular Dynamics simulations of Zika Virus NS3 helicase: Insights into RNA binding site activity” was just accepted for publication in a special issue on Flaviviruses for the journal Biochemical and Biophysical Research Communications. This study of the NS3 helicase system helped us learn more about this promising target for blocking Zika replication. The results will help guide how we analyze the virtual screens that we already performed against NS3 helicase, and the molecular dynamics simulations generated new conformations of this protein that we will use as input targets in new virtual screens that we perform as part of OpenZika.

    Additional News

    We have applied and been accepted to present OpenZika: Opening the Discovery of New Antiviral candidates against Zika Virus and Insights into Dynamic behavior of NS3 Helicase to the 46th World Chemistry Congress. The conference will be held in Sao Paulo, Brazil, on July 7-14.

    Dr. Sean Ekins has hired a postdoc and a master level scientist who will get involved with the OpenZika project. We have also started to collate literature inhibitors from Zika papers.

    Also, Drs. Sean Ekins and Carolina Andrade have offered to buy some of the candidate compounds that we identified in the virtual screens from OpenZika, so that they can be assayed in the next round of tests.


    Dr. Alex Perryman models an OpenZika shirt. Profits from the sale of OpenZika merchandise go to purchasing compounds for lab testing. (Photo by Keith Bratcher, courtesy of Rutgers University)

    Alexander L. Perryman, Ph.D., is a senior researcher (Research Teaching Specialist III) in the lab, with extensive training in computational methods in drug discovery and in the biochemical mechanisms of multi-drug-resistance in infectious diseases. He is a member of the Center for Emerging & Re-emerging Pathogens, in the Department of Pharmacology, Physiology & Neuroscience. Alex started performing research in Professor Cleo Samudzi’s X-ray crystallography lab as a freshman in the undergraduate Biochemistry program at the University of Missouri-Columbia (“Mizzou” or MU). He then became a Beckman Scholar in Professor Thomas P. Quinn’s protein structure & radiopharmaceuticals lab at MU. He received his Ph.D. in Biomedical Sciences from the University of California, San Diego (UCSD) School of Medicine (Pharmacology Department) as a Howards Hughes Medical Institute fellow in H.H.M.I. Principal Investigator J. Andrew McCammon’s lab. As a graduate student, Alex used Molecular Dynamics simulations to (a) predict a mechanism of multi-drug-resistance for “super bug” mutants of HIV protease, (b) to predict the existence of allosteric binding sites on the surface of HIV protease and then (c) to test the utility of exploiting that allosteric relationship. These predictions are now supported by an ever-growing body of experimental evidence. He also helped create the “Relaxed Complex Scheme,” which was one of the first methods to incorporate the flexibility of the target protein into docking studies of potential drug-like compounds. He conducted post-doctoral research at the California Institute of Technology (“Caltech”) as an Amgen fellow in the Division of Biology. He then became a Research Associate in Prof. Arthur J. Olson’s lab at The Scripps Research Institute (TSRI), where he ran the day-to-day operations of the FightAIDS@Home project (the largest computational drug discovery project devoted to HIV/AIDS, which runs on IBM’s World Community Grid). He also designed, led, and ran the day-to-day operations for the largest computational drug discovery project ever performed against malaria, the GO Fight Against Malaria project, also on IBM’s World Community Grid. GO FAM involved screening 5.6 million compounds against 22 different classes of drug targets (including targets from Mycobacterium tuberculosis, as well). GO Fight Against Malaria was the first academic project to ever perform over 1 billion different docking jobs. His experience is highlighted by over 24 publications and one US patent.

    In the Freundlich lab, Alex has broadened his experience by becoming an expert at developing and applying machine learning models and other ligand-based techniques to advance Mtb research, as well as projects against the ESKAPE pathogens. He has also created several machine learning models to help address key shortcomings in chemical tool discovery and drug development (such as metabolic stability, cytotoxicity, and solubility). For a change, Dr. Perryman has also been getting his hands wet–purifying proteins and performing enzyme inhibition assays, to help test his new computational predictions against Mtb targets.

    See the full article here.

    Ways to access the blog:
    https://sciencesprings.wordpress.com
    http://facebook.com/sciencesprings

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    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.
    BOINCLarge

    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.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    MyBOINC

    “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-

    FightAIDS@home Phase II

    FAAH Phase II
    OpenZika

    Rutgers Open Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    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

    faah-1-new-screen-saver

    faah-1-new

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

    IBM – Smarter Planet
    sp

     
  • richardmitnick 2:03 pm on April 6, 2017 Permalink | Reply
    Tags: , , , WCG   

    From Mapping Cancer Markers at WCG: “Mapping Cancer Markers Team Analyzes Lung Cancer Data” 

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    WCGLarge

    World Community Grid (WCG)

    By: The Mapping Cancer Markers research team
    6 Apr 2017

    Summary
    In this project update, the Mapping Cancer Markers team describes how they are analyzing 45 million of the most promising lung cancer data results, and how they have begun to disseminate their early findings.

    The Mapping Cancer Markers (MCM) project continues to process work units for the Ovarian Cancer dataset. As we accumulate these results, we continue to analyze MCM results from the previous Lung Cancer dataset. Below, we discuss one direction in which we are pursuing the analysis.

    Patterns of gene-family signatures in lung cancer

    In cancer, and human biology in general, multiple biomarkers (genes, proteins, microRNAs, etc.) can have similar patterns of activity. This may be because the genes serve redundant roles, or because the genes (or other molecules) participate together in a group to serve a biological function. A cancer signature composed of a set of specific genes may appear different than another signature composed of different, specific genes, and yet perform equivalently because the genes in each are functionally related. With this problem in mind, post-doctorate fellow Anne-Christin Hauschild is leading a study of frequently-occurring patterns (or motifs) of genes present in high-performing lung cancer gene signatures.

    1
    Illustration 1: Summary of the analysis workflow

    This project looked at the first phase results from the Lung Cancer MCM analysis, which was a systematic exploration of the entire space of potential fixed-length signatures. We began by selecting 45 million high-performing signatures derived from World-Community-Grid-computed MCM results. These are the signatures evaluated to carry the most information for lung cancer diagnosis.

    Next, we divided all genes in the lung cancer dataset into 180 clusters (gene families), where genes in each family show similar activity in the lung cancer dataset. We then labelled those top signatures with the gene families into which the genes were assigned. This gave us a set of high-performing signatures expressed as gene families instead of genes. This allowed us to treat two different gene signatures as the same gene-family signature, as long as the corresponding genes in each signature are members of the same family.

    To help understand the gene-families themselves, we can visualize each one with word clouds that describe the functions of the genes they contain, or the biological pathways they represent. We draw this information from databases such as Gene Ontology, pathDIP, or other sources.

    From there, we looked for patterns in these gene-family signatures: which families appear unusually frequently (or rarely) in high-performing signatures, or families that tend to appear multiple times in the same signature. We used Frequent-Itemset mining algorithm to discover specific patterns that occur unusually frequently in good signatures.

    2
    Illustration 2: Some gene families occur multiple times in a single signature with surprising frequency (high or low). Family 109 rarely appears multiple times. Family 12 appears surprisingly often in 9x multiples.

    3
    Illustration 3: Several important gene families, characterized by word clouds describing the genes’ molecular function annotations from the Gene Ontology database. Circles group families into common patterns found in high-performing signatures. Patterns often overlap, as in this example: one pattern containing families 3, 5, and 18 intersects with another containing families 12, 18, and 57.

    Using databases such as IID or pathDIP, we can take these patterns and examine the relationships between the gene-families they contain, so we can start to understand why certain combinations of such families carry so much information about lung cancer. We use NAViGaTOR to visualize and explore these complex sets of relationships.

    4
    Illustration 4: Relationship between 11 significant gene families (large circles) within a protein interaction network. Only the most important genes (dots, colour-coded by biological function) in each family are shown.

    We presented the preliminary results of this project to Canadian and international cancer researchers this February, in a poster at the Personalizing Cancer Medicine Conference 2017 in Toronto, Ontario. We gained many insights and ideas from discussing this early work, and we continue developing them further.

    Some of the additional, related results have been presented in other publications, including:

    Pinheiro, M., Drigo, S.A., Tonhosolo, R., Andrade, S.C.S., Marchi, F.A., Jurisica, I., Kowalski, L.P., Achatz, M.I., Rogatto, S.R., HABP2 p.G534E variant in patients with family history of thyroid and breast cancer, Oncotarget, In press.
    Citron, F., Armenia, J., Barzan, L., Franchin, G., Polesel, J., Talamini, R., Sulfaro, S., Croce, C.M., Klement, W., Pastrello, C., Jurisica, I., Vecchione, A., Belletti, B., Baldassarre, G., A microRNA signature identifies SP1 and TGFbeta pathways as potential mediators of local recurrences in head and neck squamous carcinomas, Clin Cancer Res, In press.
    Sokolina K, Kittanakom S, Snider J, Kotlyar M, Maurice P, Gandía J, Benleulmi-Chaachoua A, Tadagaki K, Wong V, Malty RH, Deineko V, Aoki H, Amin S, Riley L, Yao Z, Morató X, Otasek D, Kobayashi H, Menendez J, Auerbach D, Angers S, Pržulj N, Bouvier M, Babu M, Ciruela F, Jockers R, Jurisica I, and Stagljar I. Systematic protein-protein interaction mapping for clinically-relevant human GPCRs, Mol Sys Biol, In press.
    Yao Z, Darowski K, St-Denis N, Wong V, Offensperger F, Villedieu A, Amin S, Malty R, Aoki H, Guo H, Xu Y, Iorio C, Kotlyar M, Emili A, Jurisica I, Babu M, Neel B, Gingras AC, and Stagljar I, A global analysis of the protein phosphatase interactome, Mol Cell, in press.
    Petschnigg J, Kotlyar M, Blair L, Jurisica I, Stagljar I, and Ketteler R, Systematic identification of oncogenic EGFR interaction partners, J Mol Biol, in press.
    Rahmati, S., Abovsky, M., Pastrello, C., Jurisica, I. pathDIP: An annotated resource for known and predicted human gene-pathway associations and pathway enrichment analysis. Nucl Acids Res, 45(D1): D419-D426, 2016.
    Chehade, R., R. Pettapiece-Phillips, Salmena, L., Kotlyar, M., Jurisica, I., Narod, S. A., Akbari, M. R., Kotsopoulos, J. Reduced BRCA1 transcript levels in freshly isolated blood leukocytes from BRCA1 mutation carriers is mutation specific, Breast Cancer Res, 18(1): 87, 2016.
    Cierna, Z., Mego, M., Jurisica, I., Machalekova, K., Chovanec, M., Miskovska, V., Svetlovska, D., Hainova, K., Kajo, K., Mardiak, J., Babal, P. Fibrillin-1 (FBN-1) a new marker of germ cell neoplasia in situ, BMC Cancer, 16: 597, 2016.

    Thank you to members

    This work would not be possible without the participation of World Community Grid Members. Thank you for generously contributing CPU cycles, and for your interest in this and other World Community Grid projects.

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    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.
    BOINCLarge

    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.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    MyBOINC

    “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-

    FightAIDS@home Phase II

    FAAH Phase II
    OpenZika

    Rutgers Open Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    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

    faah-1-new-screen-saver

    faah-1-new

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

    IBM – Smarter Planet
    sp

     
  • richardmitnick 2:34 pm on March 28, 2017 Permalink | Reply
    Tags: , , WCG   

    Clean Energy from WCG: “Clean Energy Project Researchers Sharing Results and Planning for the Future” 

    WCG
    World Community Grid

    Clean Energy

    Clean Energy Project

    By: The Clean Energy Project team
    Harvard University
    28 Mar 2017

    Summary
    The Clean Energy Project team is working on publicizing their results to-date. They have wrapped up the second phase of the project, and are also making decisions about their future work with World Community Grid.

    Remember this video from a couple of years ago about the goals of the Clean Energy Project? Thanks to the many volunteers who supported this study, the researchers were able to collect an enormous amount of data, which they are now analyzing and getting ready to publish.


    The Clean Energy Project research team at Harvard would like to thank the volunteers who supported us through two phases of the project! Currently, we are getting ready to share our findings in at least one publication and a conference. We are also weighing different options for further work with World Community Grid, which might include new types of calculations on solar cells or perhaps a study with a much larger scope.

    Publishing Our Results

    We have completed our screening of non-fullerene acceptor materials for new organic photovoltaic devices. The findings were quite interesting and have kept us very busy! We describe our results in a manuscript that was submitted to the high-impact journal Energy & Environmental Science.

    Steven Lopez will travel to San Francisco to present this work at the American Chemical Society national meeting in April 2017. Alán has presented the results of the Clean Energy Project in several forums and they have helped inform the screening for other materials, such as organic flow batteries, in his research group.

    Considering our findings, we are working hard to continue developing what we have learned with this initial study. Our work may have led to the discovery of a new class of non-fullerene acceptors, with excellent properties including low production costs! We will reveal the chemical identities of these exciting derivatives when the paper is published.

    How Scientific Papers Get Published

    The process of peer-review scientific publishing is not so straightforward and can take many months, or even years in some cases.

    First, the manuscript of a paper is sent to an editor, which decides whether the work will be reviewed at all. Depending on the journal, this can be just one out of every five manuscripts received. Then, three to five experts in the field independently assess the manuscripts that are accepted for review. Each reviewer must certify that the researchers’ approach and results are novel and worth publishing.

    If the panel decides that a manuscript should be published, they will put forth suggestions and concerns that the manuscript’s authors respond to. Typically, after these concerns and edits have been addressed, the publishing agency will recommend that a paper be published. If it is to be published online, it usually become available in 1-2 weeks.

    Future Work with World Community Grid

    We have not been able to submit work units for volunteer calculation because we had been working to expand the number of molecules we will test by using a low-cost computational method to evaluate the properties of potential photovoltaic materials. With our efficient calibration scheme, this would allow us to screen 10-100 times as many candidates in the same amount of time. If this process can be fully optimized, we could begin generating these work units for volunteers. Benjamin Sanchez-Lengeling has pushed this aspect of the project forward; keep an eye on this rising star!

    However, it is also possible that we may go in a different direction altogether. Another idea we are considering is to use these efficient computational methods to catalog the properties of molecules that benefit humanity and have applications beyond clean energy. Molecular Space is vast and full of useful molecules for the world.

    We appreciate everyone’s patience while we take stock of the resources and personnel available in our lab, and make decisions about the best scientific use of the generous donations of computing time provided by World Community Grid volunteers.

    Thanks again to everyone for your support of this project over the years,

    Alán Aspuru-Guzik and Steven Lopez
    On Behalf of the CEP Team

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Harvard Clean Energy Project Database contains data and analyses on 2.3 million candidate compounds for organic photovoltaics. It is an open resource designed to give researchers in the field of organic electronics access to promising leads for new material developments.

    Would you like to help find new compounds for organic solar cells? By participating in the Harvard Clean Energy Project you can donate idle computer time on your PC for the discovery and design of new materials. Visit WorldCommunityGrid to get the BOINC software on which the project runs.

    CleanEnergyProjectPartners

    CEP runs on software from BOINC, Berkeley Open Infrastructure for Network computing.

    BOINCLarge

     
  • richardmitnick 1:48 pm on March 24, 2017 Permalink | Reply
    Tags: , , WCG   

    From Help Stop TB at WCG: “Help Stop TB Team Selects Data Analysis Tools” 

    New WCG Logo

    WCGLarge

    World Community Grid (WCG)

    By: The Help Stop TB Team
    University of Nottingham
    28 Feb 2017

    Summary
    The Help Stop TB team is hard at work analyzing the data they’ve received so far from World Community Grid. They recently chose two new data analysis tools, which will help them better understand the behavior of the bacterium which causes tuberculosis.

    Hello everyone, and thank you for contributing your computer time to Help Stop TB! We would have never completed so many simulations if it wasn’t for you!

    Background

    Help Stop TB was created to examine a particular aspect of the highly resistant and adaptable bacterium that causes tuberculosis. The bacterium has an unusual coat which protects it from many drugs and the patient’s immune system. Among the fats, sugars and proteins in this coat, the TB bacterium contains a type of fatty molecules called mycolic acids. Our project simulates the behavior of these molecules in their many configurations to better understand how they offer protection to the TB bacteria. With the resulting information, scientists may be able to design better ways to attack this protective layer and therefore develop better treatments for this deadly disease.

    Choosing Data Analysis Tools and Methods

    Since our previous mini update in November, Athina has been focusing on analysing our simulation data, and at the same time she is writing up her PhD thesis. As a team, we have now achieved our main goal, which was to come up with a robust and efficient analytical strategy. This will enable us to efficiently process the heaps of data we’re receiving from the simulations conducted by World Community Grid volunteers, and will answer our questions about mycolic acids’ conformational behaviour and its biological implications.

    The analysis protocol that we have decided on combines a variety of different analytical tools and methods. One of the tools we are using is a PCA (principal components analysis) clustering technique developed at the School of Pharmacy at the University of Nottingham. This tool has helped us categorise the shapes that mycolic acids adopt throughout the simulations. In turn, this gives us a clearer idea about which shapes are the most dominant ones.

    Figures 1 and 2 below are examples of how we are looking at the shapes of mycolic acids. These structures are important as we are looking at all the possible conformations that mycolic acids can assume in order to try to understand how those molecules work, how their conformations dictate any biological implications and/or affect the disease itself, in the hope to find any links and discover more for prevention methods.

    Because it has been shown that mycolic acids tend to demonstrate complex conformational behaviours with frequent folding and unfolding events, it is important to assess the frequency of those events. Understanding the frequency in which mycolic acids change from one folding conformation into another may help underpin important aspects of their biological behaviour.

    1
    Figure 1. Summary of a mycolic acid predominant clusters and their respective representative structures. This figure outlines the clusters’ transitions and dependency as well as their relative percentages.

    Additionally, the length of time that the molecules choose to remain in a certain adopted conformational pattern may also elucidate further biological implications. Each molecule assumes different shapes throughout its folding pathway and these shapes can be very dependent to each other. From the PCA clustering tool data, we have extracted important information regarding the dependency (Figure 1) between the different shapes the molecules assume.

    Another analytical approach that we employed was the distance matrix analysis. We created and analysed matrices (Figure 2) of the distances of all the carbon atoms along the mycolic acid chain. This method can provide further insight into the frequency of the folding events and can also help us understand more about the flexibility of each structure.

    2
    Figure 2. Distance matrices of two very different conformations of a mycolic acid. These matrices show the distances of carbon atoms along the mycolic acid chain in these two conformations, and provide a good visual idea of how different the various folding patterns are.

    We have also tested the suitability of a dihedral angle clustering tool which was developed at the Centre for Molecular Design (CMD) at the University of Portsmouth. This tool was computationally less intensive than the distance matrix analysis, but unfortunately it could not address the frequent refolding events that the mycolic acids demonstrate, thus making it challenging to extract meaningful data. However, the test cases that we analysed with this technique confirmed the predominant clusters that we had found with our PCA tools. We will now use the best choice of analysis options to build a picture for all the different mycolic acids, and will subsequently link the individual behaviour with experimental data on mycolic acid population in bacterial cell walls and their individual roles therein.

    That was all our news for now! Thank you again for your contributions, and let’s all wish good luck to Athina with her writing! Until the next time, happy crunching!

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    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.
    BOINCLarge

    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.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    MyBOINC

    “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-

    FightAIDS@home Phase II

    FAAH Phase II
    OpenZika

    Rutgers Open Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    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

    faah-1-new-screen-saver

    faah-1-new

    World Community Grid is a social initiative of IBM Corporation
    IBM Corporation
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    IBM – Smarter Planet
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  • richardmitnick 1:27 pm on March 21, 2017 Permalink | Reply
    Tags: , , , , WCG   

    From OpenZika at WCG: “OpenZika Researchers Continue Calculations and Prepare for Next Stage” 

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    By: The OpenZika research team
    21 Mar 2017

    Summary
    The OpenZika researchers are continuing to screen millions of chemical compounds as they look for potential treatments for the Zika virus. In this update, they report on the status of their calculations and their continuing work to spread the word about the project.

    Project Background

    While the Zika virus may not be getting the continuous press coverage that it received in 2015 and 2016, it is still a threat to the health of people across the globe. New infections continue to be reported in both South America and North America, and medical workers are just beginning to assess the effects of the virus on young children whose mothers were infected while pregnant.

    The search for effective treatments is crucial to stemming the tide of the virus. In addition to the OpenZika project, several other labs are doing cell-based screens with drugs already approved by the US Food and Drug Administration (FDA) agency, but few to none of the “hit” compounds that have been identified thus far are both potent enough against Zika virus and also safe for pregnant women.

    Also, there are a number of efforts underway to develop a vaccine against the Zika virus. However, vaccines do not help people who already have the infection. It will be several years before they are proven effective and safe, and before enough doses can be mass produced and distributed. And even after approved vaccines are available and distributed to the public, not all people will be vaccinated. Consequently, in the meantime and in the future, cures for Zika infections are needed.


    ZIKV NS3 helicase bound to RNA with the predicted binding modes of five approved drugs (from our second set of candidates) selected by virtual screening. These candidates are shown as surfaces with different shades of green. The identification of these candidates and the video were made by Dr. Alexander L. Perryman at RWJ Rutgers University.

    3
    Alex Perryman

    We began the analysis phase of the project by focusing on the results against the apo NS3 helicase crystal structure (apo means that the protein was not bound to anything else, such as a cofactor, inhibitor, or nucleic acid) to select our first set of candidates, which are currently being assayed by our collaborator at University of California San Diego, Dr. Jair L. Siqueira-Neto, using cell-based assays. The NS3 helicase is a component of the Zika virus that is required for it to replicate itself.

    In the second set of screening results that we recently examined, we used the new crystal structure of NS3 helicase bound to RNA as the target (see the images / animation above). Similar to the first set of candidates, we docked approximately 7,600 compounds in a composite library composed of the US Food and Drug Administration-approved drugs, the drugs approved in the European Union, and the US National Institutes of Health clinical collection library against the new RNA-bound structure of the helicase. Below are the results of this second screening:

    232 compounds passed the larger collection of different energetic and interaction-based docking filters, and their predicted binding modes were inspected and measured in detail.
    Of the compounds that were inspected in detail, 19 unique compounds passed this visual inspection stage of their docked modes.
    From the compounds that passed the visual inspection, 9 passed subsequent medicinal chemistry-based inspection and will be ordered soon.

    Status of the calculations

    In total, we have submitted 2.56 billion docking jobs, which involved the virtual screening of 6 million compounds versus 427 different target sites. We have already received approximately 1.9 billion of these results on our server. (There is some lag time between when the calculations are performed on your volunteered machines and when we get the results, since all of the results per “package” of approximately 10,000 different docking jobs need to be returned to World Community Grid, re-organized, and then compressed before sending them to our server.)

    Except for a few stragglers, we have received all of the results for our experiments that involve docking 6 million compounds versus the proteins NS1, NS3 helicase (both the RNA binding site and the ATP site), and NS5 (both the RNA polymerase and the methyltransferase domains). We are currently receiving the results from our most recent experiments against the NS2B / NS3 protease.

    A new stage of the project

    We just finished preparing and testing the docking input files that will be used for the second stage of this project. Instead of docking 6 million compounds, we will soon be able to start screening 30.2 million compounds against these targets. This new, massive library was originally obtained in a different type of format from the ZINC15 server. It represents almost all of “commercially available chemical space” (that is, almost all of the “small molecule” drug-like and hit-like compounds that can be purchased from reputable chemical vendors).

    The ZINC15 server provided these files as “multi-molecule mol2” files (that is, many different compounds were contained in each “mol2” formatted file). These files had to be re-formatted (we used the Raccoon program from Dr. Stefano Forli, who is part of the FightAIDS@Home team) by splitting them into individual mol2 files (1 compound per file) and then converting them into the “pdbqt” docking input format.

    We then ran a quick quality control test to make sure that the software used for the project, called AutoDock Vina, could properly use each pdbqt file as an input. Many compounds had to be rejected, because they had types of atoms that cause Vina to crash (such as silicon or boron), and we obviously don’t want to waste the computer time that you donate by submitting calculations that will crash.

    By splitting, reformatting, and testing hundreds of thousands of compounds per day, day after day, after approximately six months this massive new library of compounds is ready to be used in our OpenZika calculations. Without the tremendous resources that World Community Grid volunteers provide for this project, we would not even dream of trying to dock over 30 million compounds against many different targets from the Zika virus. Thank you all very much!!!

    For more information about these experiments, please visit our website.

    Publications and Collaborations

    Our PLoS Neglected Tropical Diseases paper, OpenZika: An IBM World Community Grid Project to Accelerate Zika Virus Drug Discovery, was published on October 20, and it has already been viewed over 4,000 times. Anyone can access and read this paper for free. Another research paper Illustrating and homology modeling the proteins of the Zika virus has been accepted by F1000Research and viewed > 3800 times.

    A group from Brazil, coordinated by Prof. Glaucius Oliva, has contacted us because of our PLoS Neglected Tropical Diseases paper to discuss a new collaboration to test the selected candidate compounds directly on enzymatic assays with the NS5 protein of Zika virus. They have solved two high-resolution crystal structures of ZIKV NS5, which have been recently released on the PDB (Protein Data Bank) (PDB ID: 5TIT and 5U04).

    Our paper entitled “Molecular Dynamics simulations of Zika Virus NS3 helicase: Insights into RNA binding site activity” was just accepted for publication in a special issue on Flaviviruses for the journal Biochemical and Biophysical Research Communications. This study of the NS3 helicase system helped us learn more about this promising target for blocking Zika replication. The results will help guide how we analyze the virtual screens that we already performed against NS3 helicase, and the molecular dynamics simulations generated new conformations of this protein that we will use as input targets in new virtual screens that we perform as part of OpenZika.

    These articles are helping to bring additional attention to the project and to encourage the formation of new collaborations.

    Additional News

    We have applied and been accepted to present “OpenZika: Opening the Discovery of New Antiviral candidates against Zika Virus and Insights into Dynamic behavior of NS3 Helicase” to the 46th World Chemistry Congress. The conference will be held in Sao Paulo, Brazil, on July 7-14.

    Dr. Sean Ekins has hired a postdoc and a master level scientist who will get involved with the OpenZika project. We have also started to collate literature inhibitors from Zika papers.

    Also, Drs. Sean Ekins and Carolina Andrade have offered to buy some of the candidate compounds that we identified in the virtual screens from OpenZika, so that they can be assayed in the next round of tests.

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    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.
    BOINCLarge

    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.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    MyBOINC

    “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-

    FightAIDS@home Phase II

    FAAH Phase II
    OpenZika

    Rutgers Open Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    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

    faah-1-new-screen-saver

    faah-1-new

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

    IBM – Smarter Planet
    sp

     
  • richardmitnick 2:04 pm on March 20, 2017 Permalink | Reply
    Tags: , , Major French Bank Now Supporting Humanitarian Research Through World Community Grid, SILCA, WCG   

    From WCG via HPC Wire: “Major French Bank Now Supporting Humanitarian Research Through World Community Grid” 

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    World Community Grid (WCG)

    1

    HPC Wire

    March 10, 2017
    No writer credit

    SILCA, the information technology and services arm for Crédit Agricole Group, has formally signed on to donate its surplus computer processing power to IBM’s (NYSE: IBM) World Community Grid in support of humanitarian research.

    In just its first month of participation, after installing the World Community Grid app on 1,100 employee workstations, it contributed the equivalent of three years of computing time to scientific research.

    World Community Grid is an IBM-funded and managed program that advances scientific research by harnessing computing power “donated” by volunteers around the globe. This resource is the equivalent of a virtual supercomputer that helps enable scientists to more quickly conduct millions of virtual experiments. These experiments aim to pinpoint promising drug candidates for further study.

    SILCA, which ensures the security and digital transformation of Crédit Agricole Group, first proposed this project at Crédit Agricole Group’s “Innovation Day” event, and won the company’s top award, chosen from among 60 initiatives described by the bank’s subsidiaries. Thanks to this project, SILCA will contribute to significant research studies in many areas, including Zika, tuberculosis, AIDS, Ebola, cancer and clean energy.

    For Philippe Mangematin, in charge of innovation development at SILCA, its participation is “a powerful message for Crédit Agricole to send about its commitment to a social responsibility agenda.”

    To date, World Community Grid has connected researchers to half a billion U.S. dollars’ worth of free supercomputing power. This resource to accelerate scientific discovery, partially hosted in IBM’s cloud, has been fueled by 720,000 individuals and 440 institutions from 80 countries who have donated more than 1 million years of computing time on more than 3 million desktops, laptops, and Android mobile devices. Their participation has helped identify potential treatments for childhood cancer, more efficient solar cells, and more efficient water filtration materials.

    World Community Grid is enabled by Berkeley Open Infrastructure for Network Computing (BOINC), an open source software platform developed at the University of California, Berkeley.

    Join World Community Grid today to enable your computer or Android device for a humanitarian project.

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    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.
    BOINCLarge

    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.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    MyBOINC

    “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-

    FightAIDS@home Phase II

    FAAH Phase II
    OpenZika

    Rutgers Open Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    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

    faah-1-new-screen-saver

    faah-1-new

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

    IBM – Smarter Planet
    sp

     
  • richardmitnick 2:03 pm on January 23, 2017 Permalink | Reply
    Tags: , FAAH, , HIVE, , , WCG   

    From FAAH at WCG: “Virtual Screening of the HIV-1 Mature Capsid Protein” 

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    World Community Grid (WCG)

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    Scripps Institute

    This webpage is dedicated to the virtual screening of the HIV-1 capsid protein in her mature form. This project is part of the HIVE Center and the FA@H initiative in collaboration with IBM and their World Community Grid (WCG).

    People involved in the project come from the Olson Lab in The Scripps Research Institute, and from all over the world as volunteers of the WCG. Meet them here.

    FightAidsOlsonLab@home

    For any question about the project or this webpage, please contact
    Dr. Pierrick Craveur : pcraveur@scripps.edu

    Background

    During the maturation of the HIV virus, the HIV-1 capsid protein (CA) assembles with thousands of copies to forms the capsid core [ref 1] with a characteristic conical shape (see Figure 1 and Figure 2C). This core encloses the RNA viral genome. Upon the entry of the HIV in host cells, the capsid core is released into the cytoplasm, and it dissociates in connection with the reverse transcription in a not completely understood process. This leads to the importation of DNA viral genome in the host cell’s nucleus, where it is integrated in the host DNA to finalize the infection.

    2
    Figure 1: The early phase of the HIV-1 replication cycle.
    (credit: Nature Reviews Microbiology 13, 471–483 (2015) | doi:10.1038/nrmicro3503)

    The critical role of CA protein, in early and late stages of the viral replication life cycle, has led to recent efforts on drug development, targeting the mature form of the protein. Currently, none of these molecules are used in clinic, and some face natural polymorphism and resistant mutations [ref 2]. Therefore, continued development of drugs targeting the CA protein is still needed.

    The critical role of CA protein, in early and late stages of the viral replication life cycle, has led to recent efforts on drug development, targeting the mature form of the protein. Currently, none of these molecules are used in clinic, and some face natural polymorphism and resistant mutations [ref 2]. Therefore, continued development of drugs targeting the CA protein is still needed.

    3
    Figure 2: The HIV-1 mature capsid assembly.
    (credit: Pierrick Craveur)

    Different level of the capsid protein structure

    CA protein consist of a sequence of 231 amino acids which folds into 3 different domains (Figure 2A): The N-terminal domain (N-ter), the linker, and the C-terminal domain (C-ter). This protein chain complexes with other chains to form hexamers (Figure 2B) or pentamers; which assemble together to form the fullerene-cone shape of the capsid core (Figure 2C). There are several models of the core assembly, but all are composed of ~200 hexamers, and exactly 12 pentamers.

    High Throughput Virtual Screening

    The FightAIDS@Home team is working with World Community Grid to find active compounds which could attach to the CA proteins and mediate the assembly of the capsid core. This computational experiment will be performed using the docking software AutoDock VINA [ref 3].
    Thanks to the volunteers, around 2 million molecules will be screened across ~50 conformations of the capsid protein, and hopefully lead to a reduced selection of molecules. This will be the starting point of a drug discovery process targeting the HIV-1 capsid protein.
    This computational experiment will be performed using the docking software AutoDock VINA [ref 3].
    With the support of our collaborators from the HIV Interaction and Viral Evolution (HIVE), experimental biding assays and infectivity assays will be conducted to determine if the selected compounds could be optimized as a promising drug candidate.

    4
    Figure 3: The four pockets of interest.
    (credit: Pierrick Craveur)

    Four pockets of interest

    Based on X-ray structures of CA protein, models of the core, and computational analysis of their flexibility, four pockets of interest have been selected on the surface of the hexamer assembly (see Figure 3).
    These pockets involve either one monomer (as pocket 2 along the linker domain), at the interface of two monomers (pocket 1 & 4), or at the six-fold interface (pocket 3).
    Mutagenesis experiments revealed that core stability is fine-tuned to allow ordered disassembly during early stage of virus replication cycle [ref 4]. This is why selection of compounds will be done either for molecules which could stabilize or destabilize the hexamer; assuming that both actions could have impacts on the equilibrium of the core.

    References

    Briggs, J. A. and H. G. Krausslich (2011). “The molecular architecture of HIV.” J Mol Biol 410(4): 491-500.
    Thenin-Houssier, S. and S. T. Valente (2016). “HIV-1 Capsid Inhibitors as Antiretroviral Agents.” Curr HIV Res 14(3): 270-282.
    Trott, O. and A. J. Olson (2010). “AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.” J Comput Chem 31(2): 455-461.
    Forshey, B. M., U. von Schwedler, et al. (2002). “Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication.” J Virol 76(11): 5667-5677.

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    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.
    BOINCLarge

    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.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    MyBOINC

    “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-

    FightAIDS@home Phase II

    FAAH Phase II
    OpenZika

    Rutgers Open Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    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

    faah-1-new-screen-saver

    faah-1-new

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

    IBM – Smarter Planet
    sp

     
  • richardmitnick 4:23 pm on January 10, 2017 Permalink | Reply
    Tags: 27 projects, and (as of November) 3 billion research results later, , , Twelve years, WCG   

    From WCG: “Community Achievements in 2016” 

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    World Community Grid (WCG)

    27 Dec 2016

    Summary
    We’re grateful for the volunteers and scientists who worked with us this year to launch two new research efforts, make progress on existing projects, and spread the word about volunteer computing to new audiences. Here are some of the highlights of 2016, which wouldn’t be possible without each of you.

    Two new research projects, two awards, several conferences…and volunteers around the globe whose support made all of this progress possible. Because of you, 2016 was a great year for World Community Grid! Below are a few of this year’s highlights.

    Helping Stop a Global Killer

    Tuberculosis is one of the world’s deadliest disease, killing approximately 1.5 million people every year. In March, researchers at The University of Nottingham launched Help Stop TB on World Community Grid to study the molecular structure of the bacterium that causes tuberculosis, so that scientists can learn how to overcome it.


    Access mp4 video here .

    Reaching a New Audience

    Thanks to votes from volunteers and supporters, an influential audience at South by Southwest (SXSW) learned how World Community Grid volunteers have supported humanitarian research projects since 2004, and heard how these volunteers helped scientists make a breakthrough that could bring clean water to millions. Listen to audio of our full presentation, which was given in March, or read about our experience.

    2
    Researcher Francois Grey, who was part of the Computing for Clean Water project, and program manager Juan Hindo presented the results of the project at South by Southwest 2016.

    Searching for Potential Treatments for Zika

    The Zika virus began spreading rapidly through the Americas in 2015. In 2016, it continued moving north and was also reported in Asia. There is no effective treatment for Zika, no vaccine, and the virus as been linked to serious complications, including lifelong brain-related issues for infants whose mothers contract Zika while pregnant. In response to volunteer requests, we looked for a project to fight the virus, and in May, an international team of researchers launched the OpenZika project on World Community Grid to search through millions of chemical compounds for those that may become treatments.


    Access mp4 video here .

    Getting Inspired by Changemakers

    Program manager Juan Hindo was invited to attend South by South Lawn 2016 at the White House in October. This first-time event brought together leaders in art, technology, innovation, and social change who are helping to improve the world. Read about Juan’s experience and how it inspired us to re-ssue our call for research projects that address climate change.

    4

    Winning Awards

    We appreciate awards because they recognize and raise awareness for the important work made possible by World Community Grid volunteers.

    Thanks to votes from volunteers and supporters, we were honored to receive a People’s Voice Webby Award in the Corporate and Social Responsiblity category. This award recognized our new online experience to help people learn about and join World Community Grid, which helped improve our sign-up rate. The Webby statuette traveled around the U.S. this summer and fall to spend time with each team member, as shown in the video below.

    Thank You

    Twelve years, 27 projects, and (as of November) 3 billion research results later, we are very grateful to the volunteers all over the world who are supporting basic science by donating unused computing time. Thanks for making 2016 a year of new beginnings and continued progress. Stay tuned for exciting news in early 2017!

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    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.
    BOINCLarge

    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.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    MyBOINC

    “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-

    FightAIDS@home Phase II

    FAAH Phase II
    OpenZika

    Rutgers Open Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    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

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

    IBM – Smarter Planet
    sp

     
  • richardmitnick 2:55 pm on January 7, 2017 Permalink | Reply
    Tags: , , , , WCG   

    From Uncovering Genome Mysteries at WCG: “Big Data and Big Plans: Next Steps for Uncovering Genome Mysteries” 

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    World Community Grid (WCG)

    15 Dec 2016 [Under what rock have you been hiding?]
    Wim Degrave, Ph.D.
    Laboratório de Genômica Funcional e Bioinformática Instituto Oswaldo Cruz – Fiocruz

    Summary
    World Community Grid’s role in the Uncovering Genome Mysteries project has ended, but the research team’s work continues as they analyze the results of the calculations and prepare to apply the data to medical, agricultural, and other real-world applications.

    1
    A diver collects samples from seawood off the coast of Australia. Uncovering Genome Mysteries analyzed protein sequences from a wide variety of life forms in many environments such as the ocean.

    Background

    The Uncovering Genome Mysteries project began on World Community Grid in November 2014, with the aim of analyzing protein sequences to help understand how organisms function and interact with each other and the environment. The project began with 120 million predicted protein sequences from close to 150,000 organisms. These protein sequences and organisms represent a wide variety of known or uncharacterised life forms in our biosphere. They came from organisms in samples taken from a range of environments, including water and soil, as well as on and inside plants and animals. Additionally, 70 million sequences, derived from prospective analysis of genetic information from microbial marine ecosystems from Australia were added, with the objective to add to the identification of possible functionalities of these sequences. In July 2015, we added yet another 20 million newly predicted sequences of proteins.

    Thanks to the enthusiastic contributions of more than 76,000 World Community Grid volunteers, all of these protein sequences were analyzed in approximately 24 months.

    Uncovering Genome Mysteries has been a challenging and ambitious project. Analyzing all the predicted enzymes and other proteins encoded in the genetic information known thus far from of all the organisms and life forms from our biosphere is a large task. Due to the development of new sequencing technologies for fast and cheap determination of genetic code, additional basic information will become available at an accelerating rate, making it increasingly difficult [?]to perform such a complete comparative analysis in the future.

    Our daunting task of performing close to 100 quadrillion comparisons has now been completed. The resulting data is more than 30 terabytes of compressed information (more than 150 terabytes uncompressed), even though each comparison only resulted in a single line of numbers for only the very highest probability similarities between protein sequences.

    Results to Date and Plans for the Future

    So, what is next? The research team at Fiocruz has spent the last year designing and testing new algorithms to transform the output of the comparisons with distance calculations between the genomes of the organisms included. Scientific literature cites many different ways to do this, depending on the purpose of the analysis and the views on evolutionary biology.

    The results of the Uncovering Genome Mysteries can be summarized as follows:

    More complete and precise information is now available on the structure and function of proteins encoded by living organisms in our biosphere. More proteins are being studied and experimented with each day in the thousands of laboratories around the world, and by using results from the comparison performed through the project, functional parallels can be drawn for proteins that show structural similarity between organisms. This is particularly valuable when predicted protein fragments are compared from uncharacterised organisms, for example in environmental and ecology studies, such as those originated from the laboratory of co-investigator Dr. Torsten Thomas, and his team from the Centre for Marine Bio-Innovation & the School of Biological, Earth and Environmental Sciences at the University of New South Wales, Sydney, Australia. The resulting database with these functional annotations will be made publicly available as the next version of our protein comparison database, ProteinWorldDB, in the coming months.

    Through comparison, new protein functions are discovered that can have medical, agricultural, technological or industrial applications. These can be as new biopharmaceuticals, bioinsecticides, biodegradation of waste, or enzymes for production of chemicals, but especially when part of new biochemical pathways in cells, that help laboratories to develop new green chemistry or energy production, or biosynthesis and transformation of new drugs. This also adds to the growing knowledge of biotechnology and synthetic biology.

    The group at Fiocruz has developed new ways to compare genomes from different organisms. Traditionally, such analyses consider what is conserved between genomes, resulting in distance calculations that are used for phylogenetic studies and the estimation of evolutionary relationships between organisms. However, we feel that this is only part of the picture, and the Fiocruz team designed a new algorithm that also takes differences into account. This was coupled to a new visualization method for such comparisons, resulting in a markedly faster way to add new data to the picture. We hope that this method will enable us to keep track of data from new organisms that becomes available, adding results to the growing ProteinWorld DB database.

    Thank you to all World Community Grid volunteers who supported this project, and we plan to keep in touch as we have further news about our ongoing research.

    See the full article here.

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