Folding@home

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Folding@home (förkortat FAH eller F@h) är ett distributed computing-projekt avsett för att utföra beräkningsintensiva simulationer av proteinveckning och för att förbättra metoderna som används inom området. Projektet startades 1 oktober 2000 och underhålls av Pandegruppen vid Stanford University.

Folding@home är världens kraftfullaste nätverk för distribuerade beräkningar, enligt Guiness.[1]

Projektets mål[redigera | redigera wikitext]

Avsikten med Folding@home är att åstadkomma korrekta simuleringar av proteinveckning och misslyckade veckningar i syfte att bättre förstå många sjukdomar, däribland sicklecellanemi, Alzheimers, Huntingtons sjukdom, Parkinsons sjukdom, galna ko-sjukan, cystisk fibros, osteogenesis imperfecta och cancer. Proteinveckning, hur proteiner bygger upp sin funktionella struktur, är även en av de största frågorna inom molekylär biologi. Hittills har Folding@home lyckats simulera proteinveckning i ett intervall på 5 till 10 mikrosekunder, vilket är en mycket längre simulering än vad man tidigare trodde var möjligt. En rapport från University of Illinois at Urbana-Champaign från 22 oktober 2002 konstaterar att Folding@home:s distribuerade simuleringar av proteinveckningar är riktiga.[2]

Funktion[redigera | redigera wikitext]

Folding@home använder sig inte av superdatorer för beräkningskraft utan använder flera hundratusentals persondatorer med ett speciellt klientprogram installerat. Klienten körs i bakgrunden och använder processor- och/eller grafikkortskraft som för tillfället inte används av användaren. Klienten ansluter då och då till Internet för att hämta en ny "arbetsenhet", som är datapaket som beräkningarna grundas på.

Deltagare i projektet kan ange ett speciellt användarnamn och kan på så sätt hålla koll på sina bidrag till projektet via en statistiksida på projektets hemsida.

Förutom vanliga klienter som utnyttjar datorns CPU finns även klienter som använder sig av datorns GPU samt en klient för Playstation 3.

Resultat[redigera | redigera wikitext]

Följande peer-review-granskade artiklar använder forskning från Folding@home.[3]

2000–2001[redigera | redigera wikitext]

  • M. R. Shirts and V. S. Pande. (2000). ”Screen Savers of the World, Unite!”. Science 290: ss. 1903–1904. doi:10.1126/science.290.5498.1903. PMID 17742054. 
  • Michael R. Shirts and Vijay S. Pande (2001). ”Mathematical Analysis of Coupled Parallel Simulations”. Physical Review Letters 86 (22): ss. 4983–4987. doi:10.1103/PhysRevLett.86.4983. 
  • Bojan Zagrovic, Eric J. Sorin and Vijay Pande (2001). ”b-Hairpin Folding Simulations in Atomistic Detail Using an Implicit Solvent Model”. Journal of Molecular Biology 313: ss. 151–169. doi:10.1006/jmbi.2001.5033. 

2002[redigera | redigera wikitext]

  • Stefan M. Larson, Christopher D. Snow, Michael R. Shirts, and Vijay S. Pande (2002) "Folding@home and Genome@home: Using distributed computing to tackle previously intractable problems in computational biology", Stefan M. Larson, Christopher D. Snow, Michael R. Shirts, and Vijay S. Pande. To appear in Computational Genomics, Richard Grant, editor, Horizon Press
  • Bojan Zagrovic, Christopher D. Snow, Michael R. Shirts, and Vijay S. Pande. (2002). ”Simulation of Folding of a Small Alpha-helical Protein in Atomistic Detail using Worldwide distributed Computing”. Journal of Molecular Biology 323: ss. 927–937. doi:10.1016/S0022-2836(02)00997-X. 
  • Bojan Zagrovic, Christopher D. Snow, Siraj Khaliq, Michael R. Shirts, and Vijay S. Pande (2002). ”Native-like Mean Structure in the Unfolded Ensemble of Small Proteins”. Journal of Molecular Biology 323: ss. 153–164. doi:10.1016/S0022-2836(02)00888-4. 
  • Christopher D. Snow, Bojan Zagrovic, and Vijay S. Pande (2002). ”The Trp Cage: Folding Kinetics and Unfolded State Topology via Molecular Dynamics Simulations”. Journal of the American Chemical Society 124: ss. 14548–14549. doi:10.1021/ja028604l. 

2003[redigera | redigera wikitext]

  • Vijay S. Pande, Ian Baker, Jarrod Chapman, Sidney P. Elmer, Siraj Khaliq, Stefan M. Larson, Young Min Rhee, Michael R. Shirts, Christopher D. Snow, Eric J. Sorin, Bojan Zagrovic (2003). ”Atomistic protein folding simulations on the submillisecond timescale using worldwide distributed computing”. Biopolymers 68: ss. 91–109. doi:10.1002/bip.10219. 
  • Young Min Rhee & Vijay S. Pande (2003). ”Multiplexed-Replica Exchange Molecular Dynamics Method for Protein Folding Simulation”. Biophysical Journal 84 (2): ss. 775–786. 
  • Eric J. Sorin, Young Min Rhee, Bradley J. Nakatani & Vijay S. Pande (2003). ”Insights Into Nucleic Acid Conformational Dynamics from Massively Parallel Stochastic Simulations”. Biophysical Journal 85: ss. 790–803. 
  • Bojan Zagrovic and Vijay S. Pande (2003). ”Solvent Viscosity Dependence of the Folding Rate of a Small Protein: Distributed Computing Study”. Journal of Computational Chemistry 24 (12): ss. 1432–1436. doi:10.1002/jcc.10297. 
  • Michael R. Shirts, Jed W. Pitera, William C. Swope, and Vijay S. Pande (2003). ”Extremely precise free energy calculations of amino acid side chain analogs: Comparison of common molecular mechanics force fields for proteins”. Journal of Chemical Physics 119 (11): ss. 5740–5761. doi:10.1063/1.1587119. 
  • Michael R. Shirts, Eric Bair, Giles Hooker, and Vijay S Pande (2003). ”Equilibrium Free Energies from Nonequilibrium Measurements Using Maximum-Likelihood Methods”. Physical Review Letters 91 (14). doi:10.1103/PhysRevLett.91.140601. 
  • Bojan Zagrovic & Vijay S Pande (2003). ”Structural correspondence between the alpha-helix and the random-flight chain resolves how unfolded proteins can have native-like properties”. Nature Structural Biology 10 (11): ss. 955–961. doi:10.1038/nsb995. 

2004[redigera | redigera wikitext]

  • Eric J. Sorin, Bradley J. Nakatani, Young Min Rhee, Guha Jayachandran, V Vishal, & Vijay S Pande (2004). ”Does Native State Topology Determine the RNA Folding Mechanism?”. Journal of Molecular Biology 337: ss. 789–757. doi:10.1016/j.jmb.2004.02.024. 
  • Christopher D. Snow, Linlin Qiu, Deguo Du, Feng Gai, Stephen J. Hagen, & Vijay S Pande (2004). ”Trp zipper folding kinetics by molecular dynamics and temperature-jump spectroscopy”. Proceedings of the National Academy of Sciences, USA 101 (12): ss. 4077–4082. doi:10.1073/pnas.0305260101. 
  • Young Min Rhee, Eric J. Sorin, Guha Jayachandran, Erik Lindahl, & Vijay S Pande (2004). ”Simulations of the role of water in the protein-folding mechanism”. Proceedings of the National Academy of Sciences, USA 101 (17): ss. 6456–6461. doi:10.1073/pnas.0307898101. 
  • Nina Singhal, Christopher D. Snow, and Vijay S. Pande (2004). ”Using path sampling to build better Markovian state models: Predicting the folding rate and mechanism of a tryptophan zipper beta hairpin”. Journal of Chemical Physics 121: ss. 415–425. doi:10.1063/1.1738647. 
  • L. T. Chong, C. D. Snow, Y. M. Rhee, and V. S. Pande. (2004). ”Dimerization of the p53 Oligomerization Domain: Identification of a Folding Nucleus by Molecular Dynamics Simulations”. Journal of Molecular Biology 345: ss. 869–878. doi:10.1016/j.jmb.2004.10.083. 

2005[redigera | redigera wikitext]

  • Eric J. Sorin, Young Min Rhee, and Vijay S. Pande (2005). ”Does Water Play a Structural Role in the Folding of Small Nucleic Acids?”. Biophysical Journal 88: ss. 2516–2524. doi:10.1529/biophysj.104.055087. 
  • Eric J. Sorin and Vijay S. Pande (2005). ”Exploring the Helix-Coil Transition via All-atom Equilibrium Ensemble Simulations”. Biophysical Journal 88: ss. 2472–2493. doi:10.1529/biophysj.104.051938. 
  • Eric J. Sorin and Vijay S. Pande (2005). ”Empirical Force-Field Assessment: The Interplay Between Backbone Torsions and Noncovalent Term Scaling”. Journal of Computational Chemistry 26: ss. 682–690. doi:10.1002/jcc.20208. 
  • C. D. Snow, E. J. Sorin, Y. M. Rhee, and V. S. Pande. (2005). ”How well can simulation predict protein folding kinetics and thermodynamics?”. Annual Reviews of Biophysics 34: ss. 43–69. doi:10.1146/annurev.biophys.34.040204.144447. 
  • Bojan Zagrovic, Jan Lipfert, Eric J. Sorin, Ian S. Millett, Wilfred F. van Gunsteren, Sebastian Doniach & Vijay S. Pande (2005). ”Unusual compactness of a polyproline type II structure”. Proceedings of the National Academy of Sciences, USA 102 (33): ss. 11698–11703. doi:10.1073/pnas.0409693102. 
  • Michael R. Shirts & Vijay S. Pande (2005). ”Comparison of efficiency and bias of free energies computed by exponential averaging, the Bennett acceptance ratio, and thermodynamic integration”. Journal of Chemical Physics 122. doi:10.1063/1.1873592. 
  • Michael R. Shirts & Vijay S. Pande (2005). ”Solvation free energies of amino acid side chain analogs for common molecular mechanics water models”. Journal of Chemical Physics 122. doi:10.1063/1.1877132. 
  • Sidney Elmer, Sanghyun Park, & Vijay S. Pande (2005). ”Foldamer dynamics expressed via Markov state models. I. Explicit solvent molecular-dynamics simulations in acetonitrile, chloroform, methanol, and water”. Journal of Chemical Physics 123. doi:10.1063/1.2001648. 
  • Sidney Elmer, Sanghyun Park, & Vijay S. Pande (2005). ”Foldamer dynamics expressed via Markov state models. II. State space decomposition”. Journal of Chemical Physics 123. doi:10.1063/1.2008230. 
  • Sanghyun Park, Randall J. Radmer, Teri E. Klein, and Vijay S. Pande (2005). ”A New Set of Molecular Mechanics Parameters for Hydroxyproline and Its Use in Molecular Dynamics Simulations of Collagen-Like Peptides”. Journal of Computational Chemistry 26: ss. 1612–1616. doi:10.1002/jcc.20301. 
  • Hideaki Fujutani, Yoshiaki Tanida, Masakatsu Ito, Guha Jayachandran, Christopher D. Snow, Michael R. Shirts, Eric J. Sorin, and Vijay S. Pande (2005). ”Direct calculation of the binding free energies of FKBP ligands using the Fujitsu BioServer massively parallel computer”. Journal of Chemical Physics 123. doi:10.1063/1.1999637. 
  • Nina Singhal and Vijay S. Pande (2005). ”Error Analysis and efficient sampling in Markovian State Models for protein folding”. Journal of Chemical Physics 123. doi:10.1063/1.2116947. 
  • Bojan Zagrovic, Guha Jayachandran, Ian S. Millett, Sebastian Doniach and Vijay S. Pande (2005). ”How large is alpha-helix in solution? Studies of the radii of gyration of helical peptides by SAXS and MD”. Journal of Chemical Physics 353: ss. 232–241. doi:10.1016/j.jmb.2005.08.053. 

2006[redigera | redigera wikitext]

  • Paula Petrone and Vijay S. Pande (2006). ”Can conformational change be described by only a few normal modes?”. Biophysical Journal 90: ss. 1583–1593. doi:10.1529/biophysj.105.070045. 
  • Eric J. Sorin, Young Min Rhee, Michael R. Shirts, and Vijay S. Pande (2006). ”The solvation interface is a determining factor in peptide conformational preferences”. Journal of Molecular Biology 356: ss. 248–256. doi:10.1016/j.jmb.2005.11.058. 
  • Eric J. Sorin and Vijay S. Pande (2006). ”Nanotube confinement denatures protein helices”. Journal of the American Chemical Society 128: ss. 6316–6317. doi:10.1021/ja060917j. 
  • Young Min Rhee and Vijay S. Pande (2006). ”On the role of chemical detail in simulating protein folding kinetics”. Chemical Physics 323: ss. 66–77. doi:10.1016/j.chemphys.2005.08.060. 
  • L.T. Chong, W. C. Swope, J. W. Pitera, and V. S. Pande (2006). ”A novel approach for computational alanine scanning: application to the p53 oligomerization domain”. Journal of Molecular Biology 357 (3): ss. 1039–1049. doi:10.1016/j.jmb.2005.12.083. 
  • I. Suydam, C. D. Snow, V. S. Pande and S. G. Boxer. (2006). ”Electric Fields at the Active Site of an Enzyme: Direct Comparison of Experiment with Theory”. Science 313 (5784): ss. 200–204. doi:10.1126/science.1127159. 
  • P. Kasson, N. Kelley, N. Singhal, M. Vrjlic, A. Brunger, and V. S. Pande (2006). ”Ensemble molecular dynamics yields submillisecond kinetics and intermediates of membrane fusion”. Proceedings of the National Academy of Sciences, USA 103 (32): ss. 11916–11921. doi:10.1073/pnas.0601597103. 
  • Guha Jayachandran, V. Vishal, and V. S. Pande (2006). ”Folding Simulations of the Villin Headpiece in All-Atom Detail”. Journal of Chemical Physics 124. doi:10.1063/1.2186317. 
  • Guha Jayachandran, M. R. Shirts, S. Park, and V. S. Pande (2006). ”Parallelized Over Parts Computation of Absolute Binding Free Energy with Docking and Molecular Dynamics”. Journal of Chemical Physics 125. doi:10.1063/1.2221680. 
  • C. Snow and V. S. Pande (2006). ”Kinetic Definition of Protein Folding Transition State Ensembles and Reaction Coordinates”. Biophysical Journal 91: ss. 14–24. doi:10.1529/biophysj.105.075689. 
  • S. Park and V. S. Pande (2006). ”A Bayesian Update Method for Adaptive Weighted Sampling”. Physical Review 74 (6). doi:10.1103/PhysRevE.74.066703. 
  • P. Kasson and V. S. Pande (2006). ”Predicting structure and dynamics of loosely-ordered protein complexes: influenza hemagglutinin fusion peptide”. PSB. doi:10.1142/9789812772435_0005. PMID 17992744. 
  • Erich Elsen, Mike Houston, V. Vishal, Eric Darve, Pat Hanrahan, and Vijay Pande (2006). ”N-Body simulation on GPUs”. Proceedings of the 2006 ACM/IEEE conference on Supercomputing. doi:10.1145/1188455.1188649. 

2007[redigera | redigera wikitext]

  • Guha Jayachandran, V. Vishal, Angel E. Garcıa and V. S. Pande (2007). ”Local structure formation in simulations of two small proteins”. Journal of Structural Biology 157 (3): ss. 491–499. doi:10.1016/j.jsb.2006.10.001. 
  • Adam L Beberg and Vijay S. Pande (2007). ”Storage@home: Petascale Distributed Storage”. IPDPS. doi:10.1109/IPDPS.2007.370672. 
  • J. Chodera, N. Singhal, V. S. Pande, K. Dill, and W. Swope (2007). ”Automatic discovery of metastable states for the construction of Markov models of macromolecular conformational dynamics”. Journal of Chemical Physics 126 (15). PMID 17461665. 
  • D. Lucent, V. Vishal, V. S. Pande (2007). ”Protein folding under confinement: a role for solvent”. Proceedings of the National Academy of Sciences, USA 104 (25): ss. 10430–10434. doi:10.1073/pnas.0608256104. 
  • P. M. Kasson, A. Zomorodian, S. Park, N. Singhal, L. J. Guibas, and V. S. Pande (2007). ”Persistent voids: a new structural metric for membrane fusion”. Bioinformatics. doi:10.1093/bioinformatics/btm250. 
  • P. M. Kasson and V. S. Pande (2007). ”Control of Membrane Fusion Mechanism by Lipid Composition: Predictions from Ensemble Molecular Dynamics”. PLoS Computational Biology 3 (11). doi:10.1371/journal.pcbi.0030220. 
  • D. Ensign, P. M. Kasson, and V. S. Pande (2007). ”Heterogeneity Even at the Speed Limit of Folding: Large-scale Molecular Dynamics Study of a Fast-folding Variant of the Villin Headpiece”. Journal of Molecular Biology 374 (3): ss. 806–816. doi:10.1016/j.jmb.2007.09.069. 
  • Alex Robertson, Edgar Luttmann, Vijay S. Pande (2007). ”Effects of long-range electrostatic forces on simulated protein folding kinetics”. Journal of Computational Chemistry 29 (5): ss. 694–700. doi:10.1002/jcc.20828. 
  • Nina Singhal Hinrichs and Vijay S. Pande (2007). ”Calculation of the distribution of eigenvalues and eigenvectors in Markovian state models for molecular dynamics”. Journal of Chemical Physics 126. doi:10.1063/1.2740261. 

2008[redigera | redigera wikitext]

  • Xuhui Huang, Gregory R. Bowman,and Vijay S. Pande (2008). ”Convergence of folding free energy landscapes via application of enhanced sampling methods in a distributed computing environment”. Journal of Chemical Physics 128 (20). PMID 18513049. 
  • Gregory R. Bowman, Xuhui Huang, Yuan Yao, Jian Sun, Gunnar Carlsson, Leonidas J. Guibas, and Vijay S. Pande (2008). ”Structural Insight into RNA Hairpin Folding Intermediates”. Journal of the American Chemical Society 130 (30): ss. 9676–9678. doi:10.1021/ja8032857. 
  • Nicholas W. Kelley, V. Vishal, Grant A. Krafft, and Vijay S. Pande. (2008). ”Simulating oligomerization at experimental concentrations and long timescales: A Markov state model approach.”. Journal of Chemical Physics 129 (21). doi:10.1063/1.3010881. 
  • Paula M. Petrone, Christopher D. Snow, Del Lucent, and Vijay S. Pande (2008). ”Side-chain recognition and gating in the ribosome exit tunnel”. Proceedings of the National Academy of Sciences, USA 105 (43): ss. 16549–16554. doi:10.1073/pnas.0801795105. 
  • Edgar Luttmann, Daniel L. Ensign, Vishal Vaidyanathan, Mike Houston, Noam Rimon, Jeppe Øland, Guha Jayachandran, Mark Friedrichs, Vijay S. Pande (2008). ”Accelerating Molecular Dynamic Simulation on the Cell processor and PlayStation 3”. Journal of Computational Chemistry 30 (2): ss. 268–274. doi:10.1002/jcc.21054. 

2009[redigera | redigera wikitext]

  • Peter M. Kasson and Vijay S. Pande (2009). ”Combining Mutual Information with Structural Analysis to Screen for Functionally Important Residues in Influenza Hemagglutinin”. Pacific Symposium on Biocomputing 14: ss. 492–503. PMID 19209725. 
  • Nicholas W. Kelley, Xuhui Huang, Stephen Tam, Christoph Spiess, Judith Frydman and Vijay S. Pande (2009). ”The predicted structure of the headpiece of the Huntingtin protein and its implications on Huntingtin aggregation”. Journal of Molecular Biology. doi:10.1016/j.jmb.2009.01.032. 
  • M. S. Friedrichs, P. Eastman, V. Vaidyanathan, M. Houston, S. LeGrand, A. L. Beberg, D. L. Ensign, C. M. Bruns, V. S. Pande (2009). ”Accelerating molecular dynamic simulation on graphics processing units”. Journal of Computational Chemistry. doi:10.1002/jcc.21209. PMID 19191337. 
  • D. L. Ensign and V. S. Pande (2009). ”The Fip35 WW Domain Folds with Structural and Mechanistic Heterogeneity in Molecular Dynamics Simulations”. Biophysical Journal 96 (8): ss. L53-55. PMID 19383445. 
  • V. A. Voelz, E. Luttmann, G. R. Bowman, and V.S. Pande (2009). ”Probing the nanosecond dynamics of a designed three-stranded beta-sheet with massively parallel molecular dynamics simulation”. International Journal of Molecular Sciences. 
  • A. Beberg and V. S. Pande (2009). ”Folding@home: lessons from eight years of distributed computing”. IEEE International Parallel and Distributed Processing Symposium. 
  • G. R. Bowman, X. Huang, and V. S. Pande (2009). ”Using generalized ensemble simulations and Markov state models to identify conformational states”. Methods. 
  • G. R. Bowman and V. S. Pande (2009). ”The Roles of Entropy and Kinetics in Structure Prediction”. PLoS One 4 (6): ss. e5840. doi:10.1371/journal.pone.0005840. 
  • Peter M. Kasson, Daniel L. Ensign and Vijay S. Pande (2009). ”Combining Molecular Dynamics with Bayesian Analysis To Predict and Evaluate Ligand-Binding Mutations in Influenza Hemagglutinin”. Journal of the American Chemical Society. PMID 19637916. 

Referenser[redigera | redigera wikitext]

Fotnoter[redigera | redigera wikitext]

  1. ^ ”Folding@Home recognized by Guinness World Records” (på engelska). engadget. http://www.engadget.com/2007/10/31/folding-home-recognized-by-guinness-world-records/. Läst 3 december 2009. 
  2. ^ C. Snow, H. Nguyen, V. S. Pande, and M. Gruebele. (2002). ”Absolute comparison of simulated and experimental protein-folding dynamics”. Nature 420 (6911): ss. 102–106. doi:10.1038/nature01160. PMID 12422224. 
  3. ^ ”Folding@home - papers”. http://folding.stanford.edu/English/Papers. Läst 3 december 2009.