Download Molecular Dynamics Simulations of the Purple Membrane

Interactions and Mechanisms
Controlling Assembly and Function
of Multiprotein Systems in Membranes
Michal Ben-nun
Jerome Baudry
Ana Damjanovic
Emad Tajkhorshid
Klaus Schulten
Beckman Institute, University of Illinois
http://www.ks.uiuc.edu
Thorsten Ritz
Organization of the Photosynthetic Unit
of Purple Bacteria
assembly
hn
proteins
function
molecular electronics
H+
V
Organization of the
Purple Membrane of Halobacteria
hn
V
assembly
protein
molecular electronics
H+
function
2-D crystalline organization of the purple membrane
lipids
~ 75 Å
bR monomer
Top and side views of the purple membrane
Structure of the hexagonal unit cell-1
top view
lateral view
•green,blue,red : bR monomers (Essen et al., P.N.A.S., 1998)
•grey : PGP extra-trimer lipids. (Pebay-Peyroula et al., Structure, 1999)
•purple : squalene (Luecke et al., J. Mol. Biol., 1999)
•orange : intra-trimer glycolipids (Essen et al., P.N.A.S., 1998)
•yellow : intra-trimer Phosphatidyl Glycerol Phosphate lipid
Asymmetry of the Purple Membrane
Extracellular
Blue : basic residues
Red : acidic residues
Green : polar residues
White : apolar residues
Grey : lipids
intracellular
Structure of the hexagonal unit cell-2
Hydration of the unit cell
•Internal hydration (Luecke et al., J. Mol. Biol., 1999)
•External hydration : molecular dynamics
Thermodynamics of the Purple Membrane
PM thickness
NpT simulation:
constant temperature,
variable volume
Reduction of PM
thickness during
NpT simulation
In-plane dimensions
Distribution of external water after MD
Equilibration of PM: rearrangement of water molecules
Before MD
After MD
water
protein
“c” dimension perpendicular to the membrane
Top view of PM: Water
molecules penetrate the PM
but not the protein, stop at
Arg82 & Asp96
Crystallographic water molecules
Crystallographic water
molecules in initial
structure
Asp96
Arg82
After 1 ns MD:
Crystallographic water molecules
diffuse outside PM,
except molecules located within the
Arg82 Asp96 channel (in white)
Structure of the hexagonal unit cell-3
Asp96
retinal
Arg82
External hydration (larger orange spheres) penetrates into bR up to the
Arg82 & Asp96 levels
Bacteriorhodopsin Monomer
retinal
•Simplest ion pump in biology
•Best characterized membrane protein (GPCRs)
•Simplest photosynthetic center
•Several molecular electronics applications
Molecular Dynamics Simulations of the Purple
Membrane
• Molecular dynamics simulations with NAMD2
• ~23700 atoms per unit cell
• Hexagonal unit cell
• Periodic boundary conditions in 3D (multilayers)
• NpT (constant pressure) simulations
• Particle Mesh Ewald (no electrostatic cutoff)
• ~2 weeks/ns on 4 Alpha AXP21264-500Mhz procs.
Reaction coordinates for the conical intersection:
Torsion around C13=C14 and h- vector
Torsion and
h- vector
Conical
intersection
S0 and S1 surfaces as a function of torsional angle and h- vector
Structures at the minima of S0 and S1 surfaces
and structure of the conical intersection
minima of S0
minima of S1
• Search for conical intersection started from both optimized geometries and
converged to same structure
• Bond in Å, angles in degrees, (in brackets: values at the conical intersection).
• Minima at S1 nearly coincides with lowest point of conical intersection
• SA-CASSCF(10,10) geometry optimized on ground and excited states.
Quantum Dynamics on Multiple Electronic States
Description of photoprocess of retinal in protein
Full Multiple Spawning (Todd Martinez)
Final structure of a single
quantum dynamics trajectory
Other important quantum effects:
•zero point energy
•Specific heat
•Energy relaxation
•Ben-Nun et al., Faraday
Discussion, 110, 447-462 (1998)
Does water rearrangement lead to a proton switch in bR?
Asp96
13-cis retinal
after photo-isomerization
N
Asp85
Asp212
Arg82
N
two
scenarios
N
Asp85
H+
Arg82
Water coming from cytoplasmic channel,
Arg82 “down”
Asp85
Arg82
Water coming from extracellular channel,
Arg82 “up”