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. VMD is a Tool to Think Carl Woese
Graphics,
Geometry
Genetics
Physics Lipoprotein particle HDL Ribosomes in whole cell
T. Martinez, Stanford U.
VMD
Analysis
Engine
Atomic coordinates Volumetric data,
210,000 registered VMD users!

3. Habitats of Photosynthetic Life Forms
purple bacterium

4. Photosynthesis in
Purple Bacteria
H+
ATP
cytoplasm ADP
Q ATP
synthase
light
QH2
RC bc1
LH1 e-
LH2
cytochrome c2
periplasm

5. The proteins that make up the chromatophore of
photosynthetic bacteria
LIGHT
ADP
Purple 15 LH1 ATP
Photosynthetic
Bacterium / RC
1 ATPase
Chromatophore (700 Å)
100 LH2 arrangement of constituent proteins
7 bc1

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. Components of a chromatophore

8. From Electrons to Molecules to Cells
chromato-
Photosynthetic Organelles in Purple Bacteria phores form a 11
network
J. Strümpfer and K. Schulten. Light harvesting complex II
B850 excitation dynamics. Journal of Chemical Physics,
131:225101, 2009.
purple
bacterium
M. Sener, J. Olsen, C. Hunter, and K. Schulten. Atomic level
structural and functional model of a bacterial cell
photosynthetic membrane vesicle. Proceedings National
Academy of Sciences, USA, 104:15723-15728, 2007.
chromatophore
light
harvesting
complex 2
Collaboration with EM tomography group
J. 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. 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. Graphics Performance
100
NewCartoon
VDW
Frames per second
10 Interactive use
1
nVidia GTX 470
0.1
100k 1M 10M
Number of atoms

11. VMD Demonstration

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. 20 million atom lamellar chromatophore patch
built from AFM structure, equilibrated for ~ 20 ns

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. electron transfers establish within about a hundred microseco
Electron 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. 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. Light Absorption by the Reaction Center
Johan Strumpfer
pigments

18. Light Absorption by the Reaction
Center
Excited state
relaxation
1 ms to
replenish
lost
e- transfer
electrons
rate (3 ps) -1

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
dynamics
population
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. 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. Feeding the Reaction Center with
Electronic Excitation
Feeder Chl A
must be out
of range of
electron
transfer!
10 ms to
Feeder Chl
replenish
500 ps
lost
A
66% efficiency
B
- transfer
electrons
e
(3 ps) -1
1 ns
decay

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. 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. 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. B875 Dynamics
Symmetry!
Symmetry!
2x
2x

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. LH1-RC
1 photon /
55 ms
36 ps
10 ms to
replenish
80%
idle
1 ns
decay
97% efficiency

28. Light Harvesting
Complex 2
Denser packing of pigments
B800
than LH1-RC
B850
Two major absorption
bands: 800 nm + 850 nm
Strümpfer and Schulten. JCP, (2011)
Strümpfer and Schulten. JCP. (2009)

29. B850 Dynamics
Symmetry!
Symmetry!
2x
2x
Strümpfer and Schulten. JCP, (2011)
Strümpfer and Schulten. JCP. (2009)

30. truncation = 5
B850 Transfers
91390 matrices
15 GB
10 ps
10 ps
N = 36
truncation=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. 1x(LH1-RC) + 3x(LH2)
1 photon /
20 ms
95% efficiency
10 ps
4 ps
50%
idle
Strümpfer, Sener Schulten (2012) JPC Letters.

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. Whole chromatophore membrane
Rhodospirillum Photometricum
20 M atoms
Scheuring Sturgis
Photosynth. 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. 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. generalized Förster theory
Excitation transfer
through fluorescent
resonant energy
transfer (FRET) in
photosynthetic light
harvesting

36. generalized Förster theory
K

37. generalized Förster theory

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 idle
M. 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, UIUC
on 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. 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 ps
50 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. 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 with
M 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” region
matophores [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. Photosynthetic Organelle
41

42. Acknowledgments
Johan Struempfer, UIUC
Melih Sener, UIUC
Jen Hsin, UIUC
Danielle Chandler, UIUC
Ana Damjanovic, John Hopkins U.
Ioan Kosztin, U. Missouri
Thorsten Ritz, UC Irvine
Dong Xu, U. Missouri
Xiche Hu, U., U. Toledo
Neil Hunter, U. Sheffield
John Ohlsen, U. Sheffield
Arvi Freiberg, U. Tartu
NSF
Zaida Luthey-Schulten, UIUC 42