Vision and Ultrafast Chemistry
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Transcript of Vision and Ultrafast Chemistry
Vision and Ultrafast Chemistry
ConeRod
Light
Rhodopsin
Visual signaling
G-protein signaling pathway
Visual Receptor Protein Rhodopsin
Humphrey et. al., J. Molec. Graphics, 14:33-38, 1996
Freely available, with source code from http://www.ks.uiuc.edu/Research/vmd/
Rhodopsin Bacteriorhodopsin
GPCR, vision in all species Photosynthesis, proton pump
V
H+h
assembly
protein function
molecular electronics
Organization of the Purple Membrane of Halobacteria
Baudry et al, J. Phys. Chem. (in press)
Ben-Nun et alFaraday Disc.110: 447-462 (1998)
Molnar et alJ. Mol. Struct.(in press)
Vibrational Spectroscopy (Kyoto)Vibrational Spectroscopy (Kyoto) Organic Synthesis (Rehovot)Organic Synthesis (Rehovot) Quantum Chemistry (Heidelberg)Quantum Chemistry (Heidelberg) Photophysics (Siena)Photophysics (Siena) Protein Simulation (Urbana)Protein Simulation (Urbana) Pharmacolgy (New York)Pharmacolgy (New York)
assembly
proteinfunction
Constructing and Simulating the Purple Membrane
molecular electronics
Molecular Dynamics Program Used: NAMD2
# processors
hexagonal unit cell
23700 atoms per 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.
0
64
128
192
256
0 64 128 192 256
NpT simulation: constant temperature, variable volume
Reduction of PM thickness duringNpT simulation
PM thickness
In-plane dimensions
Thermodynamics of the Purple Membrane
“c” dimension perpendicular to the membrane
Nb
of a
t om
s
Before MDAfter MD
water
protein
Distribution of external water after MD
Top view of PM: Water molecules penetrate the PM, but not the protein, stop at Arg82 & Asp96
Equilibration of PM: rearrangement of water molecules
Asp96
Arg82retinal
Color in Vision
Visual receptors of rhodopsin family are classified based on their color sensitivity
cone cells
Rhodopsin Family of Proteins
protonated Schiff base retinal (PSBR)
• Seven transmembrane helices• Retinal chromophore bound to a lysine via the Schiff base
NMeMeMeMeMeH
Color Regulation
500nm 600nm400nm
Absorption spectra of retinal in different visual receptors
Visual receptors detect light by electronic excitation of retinalat different wavelengths.
Question:How does the protein tune the absorption
spectrum of retinal?
Repellent response to blue-green light
Spectral Tuning in Archaeal Rhodopsins
sRIIbR
hRsRI
500nm 600nm
Spectral features• Absorption maximum is strongly blue-shifted (70 nm from bR).• Prominent sub-band.
Sensory Rhodopsin II (sRII)
Sequences Structures of bR and sRII
X-ray Structures of bR and sRII
Landau et al.
orange: sRII (Natronobacterium pharanois)
purple: bR (Halobacterium salinarum)
Unique opportunity to study spectral shift givenby the availability of X-ray structures.
• Structures are homologous. (e.g., all-trans retinals)• Spectra are significantly different.
Binding Sites of bR and sRIIbR
sRII
Similar structure• Aromatic residues.• Hydrogen-bond network. (counter-ion asparatates, internal water molecules)
T204A/V108M/G130S ofsRII produces only 20 nm (30%) spectral shift.
Mutagenic substitutions(Shimono et al.)
What is the main determinant(s) ofspectral tuning?
Calculation of Absorption Spectra of bR and sRII
Combined quantum mechanical/molecular mechanical (QM/MM) calculations.• Retinal is described by ab initio MO (HF/CASSCF).• Protein environment by molecular mechanics force field (AMBER94).
S2
S0
S1
S0
S1
S2
isolated in protein
Mechanism of Spectral Tuning• Electrostatic interaction between the retinal Schiff base and protein
• Electronic reorganization of retinal due to polarization of retinal’s wave function
S0
S1
S2+ +
positive charge
OC
O
Asp (Glu)
NMeMeMeMeMeH
Results
S1-S0 : 6.1 (exp. 7.2) kcal/mol. (shift of main absorption band) The shift is mainly due to electronic reorganization. S2-S1 : 1.7 (exp. 4.0) kcal/mol. (appearance of side band in sRII) Optically forbidden in bR, but a peak (side-band) appears in sRII due to intensity borrowing from the S1 state, which is optically allowed.
500nm
bRsRII
600nm
Contributions from Residues
Structural Determinants of Spectral Shift
N16 – C(Asp201: sRII) : 4.5 A
N16 – C(Asp212: bR) : 5.2 A QM/MM optimized structuresorange: sRII, purple: bR
G helix
G helix is displaced in sRII.
Distance between the Schiff base and the counter-ion is shorter.
Quantum (Wave Packets) Dynamicin protein, 1-dimensional surface
Ben-Nun et al., Faraday Discussion, 110, 447 - 462 (1998)
Rhodopsin Photodynamics
Calculation of transition amplitude
Control of Branching Ratios by Intersection Topography
On-the-fly ab initio QM/MM MD Simulation
• An analogue of retinal (three double bonds) in bR (20 QM atoms, 96 basis functions)• CASSCF (6,6) / AMBER
The Role of Conical Intersection Topographyon the Photoisomerization of Retinal
Emad Tajkhorshid
Jerome Baudry
Michal Ben-nun
$$: Beckman Institute, NSF, HFSP, NIH-NCRR
Shigehito Hayashi