Rosetta@home
3255539
225964674
2008-07-16T06:15:20Z
Emw2012
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Removed periods at the end of image captions per [[Wikipedia:MOS#Captions | MOS#Captions]]
[[Image:Rosetta_at_home_logo.png|right|thumb|250px|Rosetta@home logo]]
'''Rosetta@home''' is a [[distributed computing]] project on the [[BOINC]] platform, run by the [[David Baker (biochemist)|Baker laboratory]] at the [[University of Washington]]. With the help of over 90,000 volunteer computers processing over 66 [[TFLOPS]] on average as of [[July 1]], [[2008]],<ref>[http://boincstats.com/stats/project_graph.php?pr=rosetta BOINCstats - Rosetta@home overview] Retrieved on July 1, 2008</ref> Rosetta@home aims to computationally [[protein structure prediction| predict protein structures]] and [[Protein design| design new proteins]] to fight a range of diseases.<ref>[http://boinc.bakerlab.org/rosetta/rah_about.php What is Rosetta@home?] Introductory overview of Rosetta@home from the project website</ref>
== Computing platform ==
Both the Rosetta@home application and the [[Berkeley Open Infrastructure for Network Computing]] (BOINC) distributed computing platform are available for the [[Microsoft Windows]], [[Linux]] and [[Macintosh]] platforms (BOINC also runs on several other platforms, e.g. FreeBSD<ref name="BOINCClient">[http://boinc.berkeley.edu/download_all.php BOINC client download] List of previous, recommended, and development versions for all available platforms. Also links to third-party distributions for other platforms.</ref>). Participation in Rosetta@home requires at least a 500 MHz or higher CPU, 200 MB of free disk space, 256 MB of RAM, and Internet connectivity.<ref>[http://boinc.bakerlab.org/rosetta/rah_requirements.php Rosetta@home recommended system requirements]</ref> As of July 1, 2008, the current version of the Rosetta application is 5.98<ref>[http://boinc.bakerlab.org/rosetta/ Rosetta@home: News]. See also [http://boinc.bakerlab.org/rosetta/old_news.php Rosetta@home: News archive]</ref> and the current BOINC program version is 5.10.<ref name="BOINCClient"/>
== Project significance ==
{{further| [[Protein structure prediction]]}}
[[Image:T0281-bakerprediction overlay.png| left | thumb | 250px | The first close to atomic-level resolution, blind [[ab initio quantum chemistry methods|ab initio]] structure prediction — CASP6 target T0281. The high-resolution refinement methodology described in the text produced a model ([[Protein structural alignment|superpositioned]] in magenta) 1.6 Å [[RMSD]] from the crystal structure (blue)]]
With the completion of the [[Human Genome Project]], scientists have only a 'flat' view of the amino acid sequence, or [[primary structure]], of proteins that make up the working parts of all human cells. In order to better understand a protein's function and aid in [[Drug_design#Rational_drug_design | rational drug design]], scientists need to know the protein's 3-dimensional, [[tertiary structure]].
Protein 3D structures are currently determined experimentally through [[X-ray crystallography]] or [[nuclear magnetic resonance]] (NMR) spectroscopy. The process is slow (it can take weeks or even months to figure out how to crystallize a protein for the first time) and comes at high cost ($20,000-$100,000 USD per protein).{{Fact|date=July 2008}} Unfortunately, the rate at which new sequences are discovered far exceeds the rate of structure determination -- out of more than 6,600,000 protein sequences available in the [[NCBI]] Non-Redundant Protein database, less than 48,000 proteins' 3D structures have been solved and deposited in the [[Protein Data Bank]], the main repository for structural information on proteins.<ref>{{cite web | author=RCSB Protein Data Bank | title=Growth of Released Structures Per Year By Molecular Type: Protein Only | accessdaymonth=July 1, | accessyear=2008 | url=http://www.pdb.org/pdb/statistics/contentGrowthChart.do?content=molType-protein&seqid=100}}</ref> One of the main goals of Rosetta@home is to predict protein structures with the same accuracy as existing methods, but in a way that requires significantly less time and money.
Head scientist Prof. David Baker wrote in his [http://boinc.bakerlab.org/rosetta/forum_thread.php?id=1177#11591 Rosetta@home journal] on Mar 3, 2006:
:"The [[protein structure prediction]] problem is perhaps the longest standing problem in molecular biology. It has been known for forty years that the structures of proteins are determined by their amino acid sequences, but as recently as five or six years ago it was generally thought that the prediction problem was completely intractable as very little progress had been made. Starting about this time we showed in the [[CASP]] blind tests that with the Rosetta low resolution structure prediction method rough models could be built for small proteins that in some cases were reasonably similar in topology to the true structure, but the predicted structures were never accurate at the atomic level. We have worked for the past five years on developing high resolution refinement methods that could take these rough models and refine them to much higher accuracy. This goal remained elusive for the first few years, but about a year and a half ago we made a breakthrough and found that we could make very accurate predictions for some proteins using a trick that involves folding not only the sequence of the protein of interest but also the sequences of a large number of evolutionarily related [[Homology (biology)#Homology of sequences in genetics|homologs]]. Using this method we made the first high accuracy [[ab initio quantum chemistry methods|ab initio]] structure prediction in CASP (the last target in CASP6) and did further tests which showed accurate predictions for 6 of 16 proteins which were published in Science last year.<ref>{{cite journal | title=Toward high-resolution de novo structure prediction for small proteins | author=Bradley et al | journal=Science | year=2005 | volume=309 | issue=5742 | pages=638-642 | url=http://www.sciencemag.org/cgi/content/full/309/5742/1868 | doi=10.1126/science.1113801}}</ref>
:However, this work did not achieve the goal of predicting structure accurately from the amino acid sequence of a protein alone as we had to resort to evolutionary information. Achieving this goal has been the central aim of Rosetta@home thus far, and as I said above it is almost a "holy grail" of computational biology. So now, for quite a few proteins we are coming close to predicting structure from their amino acid sequences without any other information is pretty breathtaking."
By participating in the Rosetta@home project, volunteers help verify and develop these new protein structure prediction algorithms.
== Disease-related research ==
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Note: Attempts to find even remote links between R@H and prostate cancer (mentioned at http://boinc.bakerlab.org/rosetta/rah_medical_relevance.php) were fruitless. It initially seems that the researcher (Vanita, all her posts here: http://boinc.bakerlab.org/rosetta/forum_user_posts.php?userid=5928) worked in Baker's lab but not with R@H
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In addition to basic research in predicting protein structure, docking and design, Rosetta@home is also used in immediate disease related research.<ref name="medicalRelevance">{{cite web | title=Rosetta@home: Disease related research | url=http://boinc.bakerlab.org/rosetta/rah_medical_relevance.php}}</ref> Numerous minor research projects are described in [http://boinc.bakerlab.org/rosetta/forum_thread.php?id=2431 David Baker's Rosetta@home journal]. Other disease related work includes:
===Amyloid illnesses===
A component of the Rosetta software suite, RosettaDesign,<ref>{{cite journal | title=Native protein sequences are close to optimal for their structures | author=Kuhlman B, Baker D | journal=Proc. Natl. Acad. Sci. USA | year=2000 | volume= | issue= | pages= | url=http://www.pnas.org/content/97/19/10383.full | doi=10.1073/pnas.0511295103}}</ref> was used to accurately predict which regions of amyloidogenic proteins were most likely to make [[amyloid | amyloid-like fibrils]].<ref>{{cite journal | title=The 3D profile method for identifying fibril-forming segments of proteins | author=Thompson et al | journal=Proc. Natl. Acad. Sci. USA | year=2006 | volume=103 | issue=11 | pages=4074-4078 | url=http://www.pnas.org/content/103/11/4074.full | doi=10.1073/pnas.0511295103}}</ref> Rosetta@home has also been used to predict structures for medically-relevant amyloids, like [[amyloid beta]], in research to better understand [[Alzheimer's disease]].<ref>{{cite web | title=Rosetta@home forum: Amyloid fibril structure prediction | url=http://boinc.bakerlab.org/rosetta/forum_thread.php?id=2583&sort=6}}</ref>
===Anthrax===
Another component of Rostta, RosettaDock,<ref>{{cite journal | title=Improved side-chain modeling for protein–protein docking | author=Wang et al | journal=Protein Science | year=2005 | volume=14 | issue=5 | pages=1328-1339 | url=http://www.proteinscience.org/cgi/content/full/14/5/1328 | doi=10.1110/ps.041222905}}</ref><ref>{{cite journal | title=Protein–Protein Docking with Simultaneous Optimization of Rigid-body Displacement and Side-chain Conformations | author=Gray et al | journal=Journal of Molecular Biology | year=2003 | volume=331 | issue=1 | pages=281-299 | url=http://dx.doi.org/10.1016/S0022-2836(03)00670-3 | doi=10.1016/S0022-2836(03)00670-3}}</ref><ref>{{cite journal| title=Progress in protein-protein docking: Atomic resolution predictions in the CAPRI experiment using RosettaDock with an improved treatment of side-chain flexibility | author=Schueler-Furman et al | journal=Proteins | year=2005 | volume=60 | issue=2 | pages=187-194 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/110548114/HTMLSTART | doi=10.1002/prot.20556}}</ref> was used in conjunction with experimental methods to model interactions between three proteins -- lethal factor (LF), edema factor (EF) and protective antigen (PA) -- that make up [[anthrax toxin]]. The computational model accurately predicted docking between LF and PA, helping to establish which [[protein domain | domains]] of the respective proteins are involved the LF-PA complex. This insight was eventually used in research resulting in improved anthrax vaccines.<ref>{{cite journal | title=A model of anthrax toxin lethal factor bound to protective antigen | author=Lacy et al | journal=Proc. Natl. Acad. Sci. USA | year=2005 | volume=102 | issue=45 | pages=16409-16414 | url=http://www.pnas.org/content/102/45/16409.full | doi=10.1073/pnas.0508259102}}</ref><ref>{{cite journal | title=Human Monoclonal Antibodies against Anthrax Lethal Factor and Protective Antigen Act Independently To Protect against Bacillus anthracis Infection and Enhance Endogenous Immunity to Anthrax | author=Albrecht et al | journal=Infection and Immunity | year=2007 | volume=75 | issue=11 | pages=5425-5433 | url=http://iai.asm.org/cgi/content/full/75/11/5425 | doi=10.1128/IAI.00261-07}}</ref>
===Herpes simplex virus 1===
RosettaDock was also used to model docking between an [[antibody]] ([[immunoglobulin G]]) and a surface protein expressed by [[herpes simplex virus 1]] (HSV-1) which serves to degrade the antiviral antibody. The protein complex predicted by RosettaDock closely agreed with hard-gotten experimental models, leading researchers to conclude that the docking method has potential in addressing some of the problems that X-ray crystallography has with modeling protein-protein interfaces.<ref>{{cite journal | title=Crystal Structure of the HSV-1 Fc Receptor Bound to Fc Reveals a Mechanism for Antibody Bipolar Bridging | author=Sprague et al | journal=PLoS Biology | volume=4 | issue=6 | pages=e148 | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1450327 | doi=10.1371/journal.pbio.0040148}}</ref>
===HIV===
As part of research funded by a $19.4 million dollar grant by the [[Bill and Melinda Gates Foundation]],<ref>{{cite news | title=Gates Foundation awards $287 million for HIV vaccine research | author=Tom Paulson | publisher=Seattle
Post-Intelligencer | date=[[2006-07-19]] | url=http://seattlepi.nwsource.com/local/278100_aidsvaccine19ww.html}}</ref> Rosetta@home has been used in designing multiple possible vaccines for [[HIV | human immunodeficiency virus]] (HIV).<ref>{{cite web | title=Development of IgG1 b12 scaffolds and HIV-1 env-based outer domain immunogens capable of eliciting and detecting IgG1 b12-like antibodies | publisher=Global HIV Vaccine Enterprise | author=Liu Y et al | url=http://www.hivvaccineenterprise.org/_dwn/Oral_Sessions.pdf}}</ref><ref>{{cite web | title=David Baker's Rosetta@home journal achives (message 40756) | url=http://boinc.bakerlab.org/rosetta/forum_thread.php?id=2431&nowrap=true#40756}}</ref>
===Malaria===
In research involved with the [[Grand Challenges in Global Health]] initiative,<ref>{{cite web | title=Homing Endonuclease Genes: New Tools for Mosquito Population Engineering and Control | url=http://www.gcgh.org/ControlInsect/Challenges/GeneticStrategy/Pages/EndonucleaseGenes.aspx}}</ref> Rosetta has also been used to computationally design novel [[Intragenomic_conflict#Homing_endonuclease_genes | homing endonuclease]] proteins, which could eradicate ''[[Anopheles gambiae]]'' or otherwise render the mosquito unable to transmit [[malaria]].<ref>{{cite journal | title=Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos | author=Windbichler et al | journal=Nucleic Acids Research | year=2007 | volume=35 | issue=17 | pages=5922-5933 | url=http://nar.oxfordjournals.org/cgi/content/full/35/17/5922?ck=nck | doi=10.1093/nar/gkm632 }}</ref> Being able to model and alter protein-DNA interactions specifically, like those of homing endonucleases, gives computational protein design methods like Rosetta an important role in [[gene therapy]] (which includes possible [[cancer]] treatments).<ref name="medicalRelevance"/><ref>{{cite journal | journal=Computational redesign of endonuclease DNA binding and cleavage specificity | author=Ashworth et al | title=Computational redesign of endonuclease DNA binding and cleavage specificity | journal=Nature | year=2006 | volume=441 | url=http://www.nature.com/nature/journal/v441/n7093/full/nature04818.html | doi=10.1038/nature04818}}</ref>
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<ref>{{cite journal | title=The RosettaDock server for local protein–protein docking | author=Lyskov S, Gray JJ | journal=Nucleic Acids Research | volume=36 | issue=Web Server issue | pages=W233-W238 | url=http://nar.oxfordjournals.org/cgi/content/full/36/suppl_2/W233 | doi=10.1093/nar/gkn216}}</ref>
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==Development history and branches of Rosetta==
<!-- Deleted image removed: [[Image:Rosetta 4.98 ab-initio screenshot.png|thumb|right|Rosetta 4.98 screen saver at work, displays the 3D model of the protein in study, as it searches for lowest energy state. The guide explaining Rosetta's graphics is at http://boinc.bakerlab.org/rosetta/rah_graphics.php]] -->
Originally introduced by the Baker laboratory in 1998 as an ab initio approach to structure prediction,<ref>{{cite journal | title=Ab initio protein structure prediction of CASP III targets using ROSETTA | author=Simons et al | journal=Proteins | year=1999 | volume=37 | issue=S3 | pages=171-176 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/66005903/HTMLSTART}}</ref> Rosetta has since branched into several development streams and distinct services. More than 7 years after Rosetta's first appearance, the Rosetta@home project was released (i.e. announced as no longer [[Development_stage#Beta | beta]]) on October 6, 2005.<ref>{{cite web | title=Rosetta@home: News archive | url=http://boinc.bakerlab.org/rosetta/old_news.php}}</ref> Many of the graduate students and other researchers involved in Rosetta's initial development have since moved to other universities and research institutions, and subsequently enhanced different parts Rosetta.
[[Image:TOP7-rosetta_superposition.png| right | thumb | 250px | Superposition of Rosetta-designed model (red) onto the x-ray crystal structure (blue, PDB ID: [http://www.rcsb.org/pdb/files/1qys.pdb 1QYS]) of TOP7]]
===RosettaDesign===
RosettaDesign, a computational approach to protein design based on Rosetta, began in 2000 with a study in redesigning the folding pathway of [[Protein_G | protein G]].<ref>{{cite journal | title=Computer-based redesign of a protein folding pathway | journal=Nature Structural Biology | author=Nauli et al | year=2001 | volume=8 | pages=602-605 | url=http://www.nature.com/nsmb/journal/v8/n7/full/nsb0701_602.html | doi=10.1038/89638}}</ref> In 2002 RosettaDesign was used to design TOP7, a 93-amino acid long [[%CE%91/%CE%B2_proteins | α/β]] protein that had an overall [[Structural_Classification_of_Proteins | fold]] never before recorded in nature. This new conformation was predicted by Rosetta to within 1.2 [[Å]] [[RMSD]] of the structure determined by [[x-ray crystallography]], representing an unusually accurate structure prediction.<ref>{{cite journal | title=Design of a Novel Globular Protein Fold with Atomic-Level Accuracy | author=Kuhlman et al | journal=Science | year=2003 | volume=302 | issue=5649 | pages=1364-1368 | url=http://www.sciencemag.org/cgi/content/full/302/5649/1364 | doi=10.1126/science.1089427}}</ref> Rosetta and RosettaDesign earned widespread recognition by being the first to design and accurately predict the structure of a novel protein of such length, as reflected by the 2002 paper describing the duel approach prompting two positive letters in the journal [[Science_(journal) | ''Science'']],<ref>{{cite journal | title=Learning to Speak the Language of Proteins | author=Jones DT | journal=Science | year=2003 | volume=302 | issue=5649 | pages=1347-1348 | url=http://www.sciencemag.org/cgi/content/full/302/5649/1347 | doi=10.1126/science.1092492}}</ref><ref>{{cite journal | title=Predicting Protein Structures Accurately | author=Grothuss et al | journal=Science | year=2004 | url=http://www.sciencemag.org/cgi/content/full/304/5677/1597b | volume=304 | issue=5677 | pages=1597-1599 | doi=10.1126/science.304.5677.1597b}}</ref> and being cited by more than 240 other scientific articles.<ref>{{cite web | title=Articles citing: Kuhlman et al (2003) 'Design of a novel globular protein fold with atomic-level accuracy' | publisher=ISI Web of Science | url=http://www.sciencemag.org/cgi/external_ref?access_num=sci%3B302%2F5649%2F1364&link_type=ISI_Citing | accessdate=2008-07-10}}</ref> The visible product of that research, TOP7, was featured as the [[Protein Data Bank]]'s 'Molecule of the Month' in October 2006;<ref>{{cite web | title=October 2005 molecule of the month: Designer proteins | publisher=RCSB Protein Data Bank | url=http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb70_1.html}}</ref> a [[Structural alignment | superposition]] of the respective cores (residues 60-79) of its predicted and x-ray crystal structures are also featured in the Rosetta@home logo.<ref>{{cite web | title=Rosetta@home: Research overview | url=http://boinc.bakerlab.org/rosetta/rah_research.php}} Compare Figure 1 (right) in reference to [http://boinc.bakerlab.org/rosetta/rah_images/rosetta_at_home_logo.gif Rosetta@home logo]</ref>
Brian Kuhlman, who obtained his PhD under [[David Baker (biochemist) | David Baker]] and now researches protein design with Rosetta in his own laboratory at the [[University of North Carolina, Chapel Hill]],<ref>{{cite web | title=Kuhlman laboratory homepage | url=http://www.unc.edu/kuhlmanpg/index.htm}}</ref> offers RosettaDesign as an [http://rosettadesign.med.unc.edu/ online service].
===RosettaDock===
RosettaDock was added to the Rosetta software suite during the first [[CAPRI]] experiment in 2002 as the Baker laboratory's [[algorithm]] for [[protein-protein docking]] prediction.<ref name="CAPRI_1">{{cite journal | title=Protein-protein docking predictions for the CAPRI experiment | journal=Proteins | author=Gray JJ et al | year=2003 | volume=52 | issue=1 | pages=118-122 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/104531835/HTMLSTART | doi=10.1002/prot.10384}}</ref> In that experiment, RosettaDock made a high-accuracy prediction for the docking between [[Streptococcus_pyogenes#Virulence_factors | streptococcal pyogenic exotoxin A]] and a [[T_cell_receptor#Structural_characteristics_of_the_TCR | T cell-receptor β-chain]], as well as a medium accuracy prediction for a complex between [[porcine]] [[α-amylase]] and a [[camelid]] [[antibody]]. While the RosettaDock method only made two acceptably accurate predictions out of seven possible, this was enough to rank it seventh out of nineteen prediction methods in the first CAPRI assessment.<ref name="CAPRI_1"/>
Development of RosettaDock diverged into two branches for subsequent CAPRI rounds as Jeffrey Gray, who laid the groundwork for RosettaDock while at the [[University of Washington]], continued working on the method in his new position at [[John Hopkins University]], and members of the Baker laboratory further developed RosettaDock in Gray's absence. The two versions differed slightly in side-chain modeling, decoy selection and other areas,<ref>{{cite journal | title=CAPRI rounds 3-5 reveal promising successes and future challenges for RosettaDock | author=Daily MD et al | journal=Proteins | year=2005 | volume=60 | issue=2 | pages=181-186 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/110548131/HTMLSTART | doi=10.1002/prot.20555}}</ref><ref>{{cite journal | title=Progress in protein-protein docking: Atomic resolution predictions in the CAPRI experiment using RosettaDock with an improved treatment of side-chain flexibility | author=Schueler-Furman O et al | journal=Proteins | year=2005 | volume=60 | issue=2 | pages=187-194 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/110548114/HTMLSTART | doi=10.1002/prot.20556}}</ref> but both the Baker and Gray methods performed well in the second CAPRI assessment, placing 5th and 7th respectively out of 30 predictor groups.<ref>{{cite journal | title=Assessment of CAPRI predictions in rounds 3-5 shows progress in docking procedures | author=Mendez R et al | journal=Proteins | year=2005 | volume=60 | issue=2 | pages=150-169 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/110548130/HTMLSTART | doi=10.1002/prot.20551}}</ref> Jeffrey Gray's [http://rosettadock.graylab.jhu.edu/ RosettaDock server] is available as a free docking prediction service for non-commercial use.
In October 2006, RosettaDock was integrated into Rosetta@home. The method used a fast, crude docking model phase using only the protein backbone, followed by a slow full-atom refinement phase in which the orientation of the two interacting proteins relative to each other, as well as side-chain interactions at the protein-protein interface, were simultaneously optimized to find the lowest energy conformation.<ref>{{cite web | title=Rosetta@home forums: Protein-protein docking at Rosetta@home | url=http://boinc.bakerlab.org/rosetta/forum_thread.php?id=2395}}</ref> The vastly increased computational power afforded by the Rosetta@home network, in combination with revised "fold-tree" representations for backbone flexibility and loop modeling, made RosettaDock 6th out of 63 prediction groups in the third CAPRI assessment.<ref>{{cite journal | title=RosettaDock in CAPRI rounds 6-12 | author=Wang C et al | journal=Proteins | year=2007 | volume=69 | issue=4 | pages=758-763 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/114298694/HTMLSTART | doi=10.1002/prot.21684}}</ref><ref>{{cite journal | title=Docking and scoring protein complexes: CAPRI 3rd Edition | author=Lensink MF | journal=Proteins | year=2007 | volume=69 | issue=4 | pages=704-718 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/110548130/HTMLSTART | doi=10.1002/prot.21684}}</ref>
===Robetta===
The [http://robetta.bakerlab.org/ Robetta server] is an automated protein structure prediction service offered by the Baker laboratory for non-commercial ''ab initio'' and comparative modeling. It has participated as an automated prediction server in the biannual [[CASP]] experiments since CASP 5 in 2004, performing among the best in the automated server prediction category.<ref>{{cite journal | title=Predictions without templates: New folds, secondary structure, and contacts in CASP5 | author=Aloy P et al | journal=Proteins | year=2003 | volume=53 | issue=S6 | pages=436-456 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/106559008/HTMLSTART | doi=10.1002/prot.10546}}</ref> Robetta has since competed in CASP 6 and 7, where it did better than average among both automated server and human predictor groups<ref>{{cite journal | title=Assessment of predictions submitted for the CASP6 comparative modeling category | author=Tress M et al | journal=Protein | year=2005 | journal=Proteins | volume=61 | issue=S7 | pages=27-45 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/112097076/HTMLSTART | doi=10.1002/prot.20720}}</ref><ref>{{cite journal | title=Assessment of CASP7 structure predictions for template free targets | author=Jauch R et al | journal=Proteins | year=2007 | volume=69 | issue=S8 | pages=57-67 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/116323418/HTMLSTART | doi=10.1002/prot.21771}}</ref><ref>{{cite journal | title=Automated server predictions in CASP7 | author=Battey JND et al | journal=Proteins | year=2007 | volume=69 | issue=S8 | pages=68-82 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/116323426/HTMLSTART | doi=10.1002/prot.21761}}</ref>
==Comparison to similar distributed computing projects==
There are several distributed computed projects which have study areas similar to those of Rosetta@home, but differ in their research approach:
===Folding@home===
Of all the major distributed computing projects involved in protein research, [[Folding@home]] is the only one to not use the [[BOINC]] platform. Both Rosetta@home and Folding@home research protein misfolding diseases (e.g. Alzheimer's disease), but Folding@home does so much more exclusively. Instead of using structure- or design-based methods to predict [[amyloid]] behavior, for example, Folding@home uses [[molecular dynamics]] to model how proteins fold (or potentially misfold, and subsequently aggregate). In other words, Folding@home's strength is protein folding, while Rosetta@home's strength is protein design and prediction of structure and docking. The two projects also differ significantly in their computing power and host diversity. Averaging about 2 [[petaFLOPS]] (2000 teraFLOPS) with a host base that includes the [[Playstation 3]] and [[graphics processing unit]]s, Folding@home has more than a 30-fold advantage in computing power over Rosetta@home, which averages 66 teraFLOPS with a host base consisting only of PC-based [[CPU]]s.
===World Community Grid===
Both Phase I and Phase II of the [[Human Proteome Folding Project]] (HPF), a subproject of [[World Community Grid]], have used the Rosetta program to make structural and functional annotations of various [[genomes]].<ref>{{cite journal | title=Superfamily Assignments for the Yeast Proteome through Integration of Structure Prediction with the Gene Ontology | author=Malmstrom et al | journal=PLoS Biology | year=2007 | volume=5 | issue=4 | pages=e76 | url=http://biology.plosjournals.org/archive/1545-7885/5/4/pdf/10.1371_journal.pbio.0050076-L.pdf | doi=10.1371/journal.pbio.0050076}}</ref><ref>{{cite web | title=World Community Grid Message Board Posts: HPF -> HPF2 transition | author=Richard Bonneau | date=2006-06-26 | url=http://homepages.nyu.edu/~rb133/wcg/thread_7398.html}}</ref> Although he now uses it to create databases for biologists, Richard Bonneau, head scientist of the Human Proteome Folding Project, was active in the original development of Rosetta at David Baker's laboratory while obtaining his PhD.<ref>{{cite web | title=List of Richard Bonneau's publications | url=http://homepages.nyu.edu/~rb133/papers.html}}</ref> More information on the relationship between the HPF1, HPF2 and Rosetta@home can be found on [http://homepages.nyu.edu/~rb133/wcg/rbonneau_posts.html Richard Bonneau's website].
===Predictor@home===
Like Rosetta@home, [[Predictor@home]] specializes in protein structure prediction. Predictor@home also has plans to develop new areas for its distributed computing platform in protein design and docking (using the [[CHARMM]] package for molecular dynamics),<ref>{{cite web | title=Predictor@home: Developing new application areas for P@H | url=http://predictor.chem.lsa.umich.edu/scientific_update_cp.php#dpath}}</ref> further likening it to Rosetta@home. While Rosetta@home uses the Rosetta program for its structure prediction, Predictor@home uses the [http://www.scripps.edu/~trippm/dtasser/ dTASSER] methodology.
Other protein related distributed computing projects on [[BOINC]] include [[QMC@home]], [http://docking.cis.udel.edu/ Docking@home], [http://boinc.fzk.de/poem/index.php POEM@home], [http://boinc.bio.wzw.tum.de/boincsimap/ SIMAP], and [http://issofty17.is.noda.tus.ac.jp/ TANPAKU] (site in Japanese). [http://ralph.bakerlab.org/ RALPH@home], the '''R'''osetta@home [[Software_release_life_cycle#Alpha | '''alph'''a]] project which tests new application versions, work units, and updates before they move on to Rosetta@home, runs on BOINC as well.
== Features and Issues ==
Features related to the current version
* Since March 2006 the project uses variable run time work units, using the same raw protein data, with each unit being approximately 3 [[megabyte|MB]]. Each work unit now runs for a defined period of CPU time (with the default CPU run time being 3 hours) calculating as many predicted protein structures - termed "models" - as the computer can create during this time period. A slow PC might compute only one model, whereas a fast PC over 100 models.
* Each work unit can run for between three and 24 hours, with the exact runtime being user-configurable.
* This CPU time option was added to allow participants on dialup Internet or operating large networks of PCs or "crunching farms" to drastically reduce Internet traffic from 1 [[gigabyte|GB]] per month per Pentium 4 (running [[24/7]]) to 1/10th of that and even less.
* Users also have the option to change the frame rate and CPU use for graphics. The default frame rate is 10 frame/s.
* A new graphics version is available for Mac OS X users.
* Rosetta will consume between 40 MB and 140 MB of memory. The biggest units, which are very rare, need up to 250 MB of memory.
== See also ==
* [[Protein structure prediction]]
* [[Protein folding]]
* [[CASP]]
* [[Drug design]]
* [[Human Proteome Folding Project]]
* [[Predictor@home]]
* [[Folding@home]]
* [[SIMAP]]
* [[Grid computing]]
* [[List of distributed computing projects]]
* [[BOINC]]
== References ==
{{reflist|2}}
== External links ==
* [http://boinc.bakerlab.org/rosetta/ Rosetta@home] Project website
* [http://ralph.bakerlab.org/ RALPH@home] Website for Rosetta@home alpha testing project
* [http://boinc.bakerlab.org/rosetta/forum_thread.php?id=1177&sort=5 David Baker's Rosetta@home journal]
* [http://boincstats.com/stats/project_graph.php?pr=rosetta BOINCstats - Rosetta@home] Detailed contribution statistics
* [http://www.youtube.com/watch?v=GzATbET3g54 Rosetta@home video on YouTube] Overview of Rosetta@home given by David Baker and lab members
* [http://boinc.berkeley.edu/ BOINC] Main page for the BOINC platform. Includes platform overview; guide for BOINC installation and attaching to Rosetta@home
'''Online Rosetta services'''
* [http://robetta.bakerlab.org/ Robetta] Protein structure prediction server
* [http://rosettadesign.med.unc.edu/ RosettaDesign] Protein design server
* [http://rosettadock.graylab.jhu.edu/ RosettaDock] Protein-protein docking server
{{BOINC topics}}
[[Category:Berkeley Open Infrastructure for Network Computing]]
[[Category:Bioinformatics]]
[[Category:Distributed computing projects]]
[[Category:Protein structure]]
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