Towards Cell Scale Molecular Dyamics - K. Schulten, July 2012

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Towards Cell Scale Molecular Dyamics - K. Schulten, July 2012

  1. 1. Towards Cell Scale Molecular Dynamics Simulations with VMD and NAMD - Demonstrated for the Light-Harvesting Apparatus of Purple Photosynthetic Bacteria Klaus Schulten Lectures Summer School July 2012 Center for Physics of Living Cells Theoretical and Computational Biophysics Group Center for Biomolecular Modeling and Bioinformatics Department of Physics Beckman Institute U. Illinois at Urbana-Champaign
  2. 2. VMD is a Tool to Think Carl Woese Graphics, Geometry GeneticsPhysics Lipoprotein particle HDL Ribosomes in whole cell T. Martinez, Stanford U. VMD Analysis EngineAtomic coordinates Volumetric data, 210,000 registered VMD users!
  3. 3. Habitats of Photosynthetic Life Forms purple bacterium
  4. 4. Photosynthesis in Purple Bacteria H+ ATPcytoplasm ADP Q ATP synthase light QH2 RC bc1 LH1 e- LH2 cytochrome c2periplasm
  5. 5. The proteins that make up the chromatophore of photosynthetic bacteria LIGHT ADP Purple 15 LH1 ATPPhotosynthetic Bacterium / RC 1 ATPase Chromatophore (700 Å) 100 LH2 arrangement of constituent proteins 7 bc1
  6. 6. Chromatophore Structure structure of building blocks (X-ray, NMR, EM) LH2 (27 BChls) LH1-RC (dimer) (64 BChls) bc1 complex Melih Sener ATP synthase long range order and composition(AFM, EM, LD, gel electrophoresis) (Bahatyrova et al., Nature, 2004.)dynamics/function (spectroscopy) (Arvi Freiberg, U. Tartu) Sener, Olsen, Hunter, Schulten, PNAS, 2007; Sener, Strumpfer, Timney, Freiberg, Hunter, Schulten, Biophys. J., 2010.
  7. 7. Components of a chromatophore
  8. 8. From Electrons to Molecules to Cells chromato-Photosynthetic Organelles in Purple Bacteria phores form a 11 networkJ. Strümpfer and K. Schulten. Light harvesting complex IIB850 excitation dynamics. Journal of Chemical Physics,131:225101, 2009. purple bacteriumM. Sener, J. Olsen, C. Hunter, and K. Schulten. Atomic levelstructural and functional model of a bacterial cellphotosynthetic membrane vesicle. Proceedings NationalAcademy of Sciences, USA, 104:15723-15728, 2007. chromatophore lightharvestingcomplex 2 Collaboration with EM tomography groupJ. Koepke, X. Hu, C. Muenke, K. Schulten, and H. Michel.The crystal structure of the light harvesting complex II of W. Baumeister, MPI Martinsried(B800-850) from Rhodospirillum molischianum. Structure,4:581-597, 1996. (with L. Fitting-Kourkoutis, E. Villa)
  9. 9. Chromatophore Size 10 Ångstrom pigment molecule ( 4,000) 100x LH2 + 20x (LH1-RC)2 + 10x bc1 + 1x ATPsynthase 4,000,000 atoms + lipids + water + ions 100,000,000 atoms 700 Ångstrom
  10. 10. Graphics Performance 100 NewCartoon VDWFrames per second 10 Interactive use 1 nVidia GTX 470 0.1 100k 1M 10M Number of atoms
  11. 11. VMD Demonstration
  12. 12. Chromatophore Exists in Different Forms Rhodobacter sphaeroides Rhodospirillum photometricum spherical planar Reviews Sener, Strümpfer, Hsin, Chandler, Hunter, Scheuring and Schulten. ChemPhysChem, 2011 Strümpfer, Hsin, Sener, Chandler and Schulten. in Molecular Machines , World Scientific, 2011
  13. 13. 20 million atom lamellar chromatophore patch built from AFM structure, equilibrated for ~ 20 ns
  14. 14. Key Energy Conversion Step in Photosynthesis Charge (electron) transfer in the RC electron transfer is controlled through coupling to thermal motion of protein! The coupling is described through so- called polaron theory that accounts for a strong temperature effect. RC D. Xu and K. Schulten. Chemical Physics, 182: 91--117, 1994.
  15. 15. electron transfers establish within about a hundred microsecoElectron Transfer Is Q− + SP+. to Thermal Motion Coupled 2 of Protein Matrix Relaxation rate Figure 1: (a) Cartoon representation of the photosynthetic react outline. (b) Surface outline of the reaction center showing bacteri and Chl4 ) in green, bacteriopheophytins (Ph1 and Ph2 ) in orange a The central bacteriochlorophylls, Chl1 and Chl2 , form the so-calle structure of a BChl. energy gap from MD A chlorophyll under bright daylight conditions would ab energy gap correlation functionin the actual dark habitat of purple bacteria second, fewer still As a result, the RC would be idling most of the time, had rms deviation of energy gapsystem of pigments. This 15 evolved a feeder feeder system com external BChls that funnel electronic excitation to the RC th D. Xu and K. Schulten. Chemical Physics, 182: 91--117, 1994.
  16. 16. Electron Transfer Is Coupled to Thermal Motiona hundred microsec electron transfers establish within about Q− + SP+ . of Protein Matrix 2 Relaxation rate Temperature Dependence of Figure 1: Electron Transfer Rate (a) Cartoon representation of the photosynthetic reac outline. (b) Surface outline of the reaction center showing bacter and Chl4 ) in green, bacteriopheophytins (Ph1 and Ph2 ) in orange a The central bacteriochlorophylls, Chl1 and Chl2 , form the so-call structure of a BChl. energy gap correlation chlorophyll under A function bright daylight conditions would ab quantum coherence! second, fewer still in the actual dark habitat of purple bacteria rms deviation of energy gapRC would be idling most 16 the time, had As a result, the of evolved a feeder system of pigments. This feeder system co D. Xu and K. Schulten. Chemical Physics, 182: 91--117, 1994. external BChls that funnel electronic excitation to the RC t
  17. 17. Light Absorption by the Reaction Center Johan Strumpferpigments
  18. 18. Light Absorption by the Reaction Center Excited state relaxation 1 ms to replenish lost e- transfer electrons rate (3 ps) -1
  19. 19. 1.1 Cherepy et al. 1997 Experiment 1 HEOM 0.9 0.8 Absorption Excitons Spectrum Absorption (a.u.) 0.7 0.6 0.5 at 300 K 0.4 0.3 0.2 P B H 0.1 with static disorder 0 10500 11000 11500 12000 12500 13000 13500 14000 -1 Energy (cm ) B-H oscillations ~ Lee et al. Science (2007) 1 PL BL HL PM BM HM Excitons Special pair dynamicspopulation 0.5 90% populated in equilibrium 0 0 0.2 0.4 0.6 0.8 1 5 10 time (ps) Strümpfer Schulten (2012) JCP.
  20. 20. Feeding the Reaction Center with maximum Electronic Excitation absorption ~ 1 photon / 300 ms Excited state 10 ms to relaxation replenish 97% lost e- transfer idle electrons rate (3 ps) -1
  21. 21. Feeding the Reaction Center with Electronic Excitation Feeder Chl Amust be out of range of electron transfer! 10 ms toFeeder Chl replenish 500 ps lost A 66% efficiency B - transfer electrons e (3 ps) -1 1 ns decay
  22. 22. Feeding the Reaction Center with Electronic Excitation: Special Pair Doubles Through Exciton Coupling its Low Energy Oscillator Strength - Quantum Coherence Exciton states 2-fold symmetry Oscillator strength = 2d2 Strümpfer, Sener Schulten (2012) JPC Letters.
  23. 23. Feeding the Reaction Center with Electronic Excitation 1 photon / 300 ms 10 ms to Feeder Chl replenish 300 ps lost A 80% efficiency B 97% - transfer idle electrons e (3 ps) -1 1 ns decay
  24. 24. Light Harvesting Complex 1 ring of 32 BChls = much higher rate of photon absorption than RC what about excitation dynamics + LH1-RC transfer times?
  25. 25. B875 Dynamics Symmetry! Symmetry! 2x 2x
  26. 26. B875-RC Transfer kinetic fit 36 ps 8 ps HEOM truncation = 5 111,930 matrices = 20 GB N = 38 Strümpfer Schulten (2012) JCP.
  27. 27. LH1-RC 1 photon / 55 ms 36 ps 10 ms to replenish 80% idle 1 ns decay 97% efficiency
  28. 28. Light Harvesting Complex 2 Denser packing of pigmentsB800 than LH1-RC B850 Two major absorption bands: 800 nm + 850 nm Strümpfer and Schulten. JCP, (2011) Strümpfer and Schulten. JCP. (2009)
  29. 29. B850 Dynamics Symmetry! Symmetry! 2x 2x Strümpfer and Schulten. JCP, (2011) Strümpfer and Schulten. JCP. (2009)
  30. 30. truncation = 5 B850 Transfers 91390 matrices 15 GB 10 ps 10 ps N = 36truncation=5 truncation=3 316251 matrices 97 GB 1326 matrices 50 MB 4 ps 18 ps N = 50 Strümpfer Schulten (2009) JCP; Strumpfer Schulten (2012) JCTC.
  31. 31. 1x(LH1-RC) + 3x(LH2) 1 photon / 20 ms 95% efficiency 10 ps 4 ps 50% idle Strümpfer, Sener Schulten (2012) JPC Letters.
  32. 32. Whole chromatophore membrane Rhodospirillum Photometricum Scheuring Sturgis Photosynth. Res. (2009) 20 Million atoms Simulated with NAMD 2.9 on Blue Waters 40 ns so far Chandler, Strümpfer, Sener Schulten. (2012) In preparation.
  33. 33. Whole chromatophore membrane Rhodospirillum Photometricum 20 M atoms Scheuring SturgisPhotosynth. Res. (2009) Transfer rates from HEOM: 24 hours x 32 processors x 114 pairs = 87,000 CPU-hours using PHI Chandler, Strümpfer, Sener Schulten. (2012) In preparation.
  34. 34. Whole chromatophore membrane Rhodospirillum Photometricum 20 M atoms HEOM: Efficiency 90.5 %; RCs rarely idle Lifetime 94.9 ps Scheuring Sturgis Simpler Description Photosynth. Res. (2009) 1 photon / generalized Förster theory: Quantum yield 90.3 % 2 ms Lifetime 97.3 ps Chandler, Strümpfer, Sener Schulten. (2012) In preparation.
  35. 35. generalized Förster theory Excitation transfer through fluorescent resonant energy transfer (FRET) in photosynthetic light harvesting
  36. 36. generalized Förster theory K
  37. 37. generalized Förster theory
  38. 38. Architecture of the Vesicle Low light configuration (100 microeinstein): High light configuration (1500 microeinstein): B850:B875 ratio → 1.9:1.0 B850:B875 ratio → 1.3:1.0 LH2:RC ratio → 2.8:1 LH2:RC ratio → 2:1 LH1RC dimers: 26 avg. lifetime: 50 ps LH2s: 107 q. yield: 95%, RCs rarely avg. lifetime: 43 ps idle q. yield: 96%, RCs rarely idleM. Sener, J. D. Olsen, C. Ne.Hunter, and K.Schulten. Atomic level structural and functional model of a bacterial photosynthetic membrane vesicle. Proc.Natl. Acad.Sciences, USA, 104:15723-15728, 2007; M. Sener, J. NIH Resource for Macromolecular Modeling and Bioinformatics Strumpfer, J. A. Timney, Ar.Freiberg, C. N. Hunter, and K. Schulten. Photosynthetic vesicle architecture and constraints Beckman Institute, UIUCon efficient energy harvesting. Biophysical Journal, 99:67-75, 2010; J. Strümpfer, J. Hsin, M. Sener, D. Chandler, and K. Schulten. The light-harvesting apparatus in purple http://www.ks.uiuc.edu/photosynthetic bacteria, introduction to a quantum biological device. In Benoit Roux, editor, Molecular Machines, chapter 2, pp. 19-48. World Scientific Press, 2011.
  39. 39. Inter-Complex Transfer Times Calculations of the inter-complex transfer times distance dependence for LH2-LH2, Slow Medium Fast LH1-LH1 and LH2-LH1 using Förster theory. 50 ps50 ps limit: 17 Å 50 ps limit for excitation 21 Å transfer: transfer needs to be fast compared to excitation life time of ~ 1 ns! 23 Å NIH Resource for Macromolecular Modeling and Bioinformatics Beckman Institute, UIUC http://www.ks.uiuc.edu/
  40. 40. Inter-Complex Transfer Times Permit Quinone Passage Protein separation limits for 50 ps transfer time: ting of Biomolecular Systems Klaus Schulten LH2-LH2: 17 Å t containing different “micro-environments” to study the interactions of pufX LH1-LH1: 21 Å with different parts of the system. sly mentioned, chromatophores come in various shapes, e.g. lamellar folds (as LH2-LH1: 23 Å by the flat membranes of Aim 3.1 - Aim 3.3) or small spherical vesicles. simulate a spherical chromatophore from Rb. sphaeroides (Aim 3.4), con- LH1-RC dimeric complexes, and bc1 complexes, arranged in agreement withM data [27]. Though some Rb. sphaeroides chromatophores may exist as iso- many are connected to the inner membrane or to neighboring chromatophores. g “neck” regions are of particular interest, as it has been proposed that the and/or ATP synthases, whose locations in the chromatophore are to-date ld inhabit these regions. We propose to simulate a system containing two matophores connected by such a “neck” region (Aim 3.5), in order to study atophore proteins are affected by different membrane curvature environments. is especially relevant to the study of the bc1 complexes, as it has been pro- quinone bc1 s might inhabit such negative-curvature environments as the “neck” regionmatophores [31]. passage M. Sener, J. Strumpfer, and K. Schulten. Biophysical J. 99: 67-75 (2010) NIH Resource for Macromolecular Modeling and Bioinformatics Beckman Institute, UIUC http://www.ks.uiuc.edu/
  41. 41. Photosynthetic Organelle 41
  42. 42. AcknowledgmentsJohan Struempfer, UIUCMelih Sener, UIUCJen Hsin, UIUCDanielle Chandler, UIUCAna Damjanovic, John Hopkins U.Ioan Kosztin, U. MissouriThorsten Ritz, UC IrvineDong Xu, U. MissouriXiche Hu, U., U. ToledoNeil Hunter, U. SheffieldJohn Ohlsen, U. SheffieldArvi Freiberg, U. Tartu NSF Zaida Luthey-Schulten, UIUC 42

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