Same chromophore

1
Same chromophore different absorption maximum
Length of the conjugation Electrostatic
interaction with the binding pocket Steric
interaction with the protein Protonation /
deprotonation
2
Same chromophore different absorption maximum
Length of the conjugation Shorter chain (blue
shift) Longer chain (red shift)
Longer wavelength
Short wavelength
3
Same chromophore different absorption maximum
Electrostatic interaction with the binding
pocket BLUE SHIFT (shorter wavelengths) -
Ground state stabilization - Excited state
destabilization


S1
S1
S1
S1
S0
S0
S0
S0
4
Same chromophore different absorption maximum
Electrostatic interaction with the binding
pocket RED SHIFT (longer wavelengths) -
Ground state destabilization - Excited state
stabilization


S1
S1
S1
S0
S0
S1
S0
S0
Very important
5
Same chromophore different absorption maximum
Steric interaction with the protein Twisting
the bonds in the backbone (blue
shift) Straightening the backbone (red shift)
Bacteriorhodopsin (568 nm)
Rhodopsin (500 nm)
6
Same chromophore different absorption maximum
Protonation / deprotonation
UV vision birds, honeybee
Strong blue shift
7
Isomerization triggers the biological response
Light
S1
S0
Response
Isomerization
8
Isomerization triggers different cellular
responses
Light
S1
Ion pump
energy
S0
Transducer activation
signaling
G-protein activation
Isomerization
9
Variety of responses to retinal isomerization
Rhodopsin
bacteriorhodopsin
Sensory rhodopsin
G-protein activation
transducer activation
ion pump
10
Rhodopsin
Light
G-protein signaling pathway
11
Rhodopsin Photocycle
Biologically active
12
Rhodopsin Photocycle
13
Rhodopsin Architecture
14
Signaling pathway of rhodopsin
G-proteins
Rhodopsin (effective
signaling)
Lipid molecules
15
G-proteins animation
16
G-protein coupled receptors

• More than 1000 types of receptor specific for
• odorants
• Photon
• Neurotransmitter
• Hormones
• Calcium
• Peptides

50 of drugs in the market act on GPCRs, which
are very difficult to crystallize ?
Importance of rhodopsin structure
17
Simulation of rhodopsin in membrane
Protein pdb file, 1HZX Lipids POPC bilayer
(artificial) Total 40,000 atoms NAMD2,
CHARMm27, PME 1 ns equilibration, 10 ns
relaxation after isomerization
18
(No Transcript)
19
Embedding the protein in membrane
1. Tyrosine residues 2. Palmitoyls connected to
Cys322 and Cys323
20
Inducing isomerization
500 nm 50 kcal/mole
21
Retinal Charge Distribution
QM/MM derived partial atomic charges
22
In the ground state, the ring of the chromophore
blocks the rotation of helix VI
23
Retinal Isomerization
Twist Propagation
24
In the ground state, the ring of the chromophore
blocks the rotation of helix VI
25
Text book figures not quite right!
26
Retinal Isomerization
Decoupling of Trp265 and the b-ionone ring
27
Rhodopsin
Bacteriorhodopsin
Isomerization 11-cis ? all-trans
Isomerization all-trans ? 13-cis
28
Isomerization Barriers and bond selectivity
Twisted bonds in Rh
Twisted bonds in bR
29
Counterion and bond selectivity
counterions in Rh
counterions in bR