Embed Size (px)
Citation preview
12131416262728303132374041448693949798101
103
110
113
114
117
118
120
121
122
124
125
167
168
170
171
176
178
179
181
182
183
185
186
187
188
189
190
191
192
193
194
203
204
206
207
208
210
211
212
261
264
265
266
267
268
269
270
271
272
273
275
276
284
285
286
287
288
289
291
292
293
295 Retinal Contacts
Dar
k R
hod
Met
a I
Met
a-II
00.2
0.4
0.6
0.8
1
12131416262728303132374041448693949798101
103
110
113
114
117
118
120
121
122
124
125
167
168
170
171
176
178
179
181
182
183
185
186
187
188
189
190
191
192
193
194
203
204
206
207
208
210
211
212
261
264
265
266
267
268
269
270
271
272
273
275
276
284
285
286
287
288
289
291
292
293
295 Retinal Contacts
Dar
k R
hod
Met
a I
Met
a-II
00.2
0.4
0.6
0.8
1
• 7
tra
nsm
em
bra
ne (
7T
M) α
-heli
cal
p
rote
ins
• 8
00
GP
CR
s in
th
e h
um
an
gen
om
e
• B
ind
ing
of
G p
rote
in t
o t
he a
cti
ve f
orm
of
t
he r
ecep
tor
ind
uces:
-
Con
form
ati
on
al
ch
an
ge
-
Sig
nal
tran
sdu
cti
on
acro
ss m
em
bra
ne
-
Sig
nali
ng
casc
ad
e
• B
iom
ed
icall
y r
ele
van
t -
More
th
an
30
% d
rug
s ta
rget
GP
CR
s• R
hod
op
sin
is
the m
am
mali
an
dim
- l
igh
t re
cep
tor
-
Reti
nal:
covale
ntl
y b
ou
nd
-
11
-cis
: in
vers
e a
gon
ist
-
All
-tra
ns:
ag
on
ist
•B
ox
size
: 7
4 Å
x 7
4 Å
x 9
0Å
•F
orc
efi
eld
: C
HA
RM
M2
7/3
6 -
Reti
nal
para
mete
rs o
bta
ined
fr
om
th
e F
ell
er
lab
•E
nse
mb
le:
NPγT
-
γ =
30
dyn
/cm
• H
eli
x 6
pri
nci
pal
axi
s co
sin
e
w
ith
mem
bra
ne n
orm
al
-
Cyt
op
lasm
ic h
alf
of
the h
eli
x
- O
psi
n a
nd
Meta
II
more
til
ted
,
b
road
er
ran
ge
• O
ther
lig
an
ds
-
Bett
er
ag
on
ists
-
Weaker
inve
rse a
gon
ists
• E
xten
d a
ccess
ible
tim
esc
ale
s w
ith
sim
ple
mod
els
- S
tru
ctu
re-b
ase
d p
ote
nti
als
- T
ran
siti
on
s in
eq
uil
ibri
um
Giv
en
th
eir
fu
nct
ion
as
tran
du
cers
of
mole
cula
r si
gn
als
acr
oss
th
e
cell
m
em
bra
ne,
G p
rote
in-c
ou
ple
d r
ece
pto
rs (
GP
CR
s) c
on
stit
ute
a m
ajo
r ta
rget
for
dru
gs
in a
wid
e v
ari
ety
of
ph
ysio
log
ical
scen
ari
os.
Un
ders
tan
din
g t
he
cou
rse o
f st
ruct
ura
l tr
an
siti
on
s th
at
all
ost
eri
call
y m
od
ula
te t
heir
act
ivati
on
is
th
ere
fore
fu
nd
am
en
tal
tow
ard
s im
pro
vin
g r
ati
on
al
dru
g d
esi
gn
. H
ere
, w
e
an
aly
ze
un
bia
sed
m
icro
seco
nd
-sca
le
all
-ato
m
mole
cula
r d
ynam
ics
sim
ula
tion
s to
ch
ara
cteri
ze
dis
tin
ct
en
sem
ble
s of
the
class
A
G
PC
R
rhod
op
sin
th
at
corr
esp
on
d t
o b
oth
act
ive-
an
d i
nact
ive-l
ike c
on
form
ati
on
s,
in
the
pre
sen
ce
an
d
ab
sen
ce
of
the
lig
an
d.
By
mon
itori
ng
th
e
lig
an
d's
ori
en
tati
on
an
d i
nte
ract
ion
s w
ith
in t
he b
ind
ing
pock
et,
we s
how
th
at
reti
nal
ad
op
ts
hete
rog
en
eou
s co
nfo
rmati
on
s th
at
are
co
nsi
sten
t w
ith
en
sem
ble
-d
ep
en
den
t d
ynam
ics.
• P
CA
calc
ula
ted
on
ag
gre
gate
b
asi
s se
t
- A
ll 5
en
sem
ble
s
- T
ran
smem
bra
ne Cα
's o
nly
-
Tra
ject
ori
es
dow
nsa
mp
led
to 5
ns
reso
luti
on
• A
vera
ge d
isp
lace
men
t b
y e
nse
mb
le
- P
C1
dis
tin
gu
ish
es
act
ive-l
ike
fro
m i
nact
ive
-
Am
pli
tud
e o
f fl
uct
uati
on
s:
d
ivers
ity
• S
yste
m s
ize:
~4
6,0
00
ato
ms
-
12
3 S
DP
E l
ipid
s -
~ 8
,00
0 w
ate
rs -
10
0 m
M N
aC
l
• I
nte
rnal
solv
ati
on
- H
-bon
din
g p
att
ern
s b
y en
sem
ble
‧ W
ate
r an
d s
alt
• L
ipid
-pro
tein
in
tera
ctio
ns
• P
red
ict
2H
NM
R s
pect
ra f
or
r
eti
nal
• E
nh
an
ced
sam
pli
ng
usi
ng
M
ark
ov
Sta
te M
od
els
• T
herm
ost
at:
Lan
gevi
n -
31
0 K
-
1 b
ar
•E
lect
rost
ati
cs:
PM
E• V
DW
cu
toff
: 1
0 Å
•T
imest
ep
: 2
fs
-
RA
TT
LE
• S
oft
ware
: -
NA
MD
2.8
-
Blu
eG
en
e/Q
• E
nse
mb
le p
roje
cted
on
to
P
C1
an
d P
C2
- E
very
dot
rep
rese
nts
a s
ing
le
st
ruct
ure
in
th
e c
orr
esp
on
din
g
en
sem
ble
• O
psi
n o
verl
ap
s w
ith
all
fou
r en
-
sem
ble
s• D
ark
Rh
od
an
d M
eta
II
are
com
pact
• M
eta
I e
xplo
res
som
e u
niq
ue
s
tate
s• O
ne r
ep
rese
nta
tive
tim
e
s
eri
es
per
en
sem
ble
- R
esi
du
e n
um
ber
colo
red
by
heli
x
- E
nse
mb
le-d
ep
en
den
t in
tera
ctio
ns
-
Con
tact
s va
ry o
n t
he t
imesc
ale
of
hu
nd
red
s of
ns
• A
vera
ge o
ccu
pan
cy
- R
esi
du
e n
um
ber
colo
red
by
heli
x
-
Meta
I i
s th
e m
ost
hete
rog
en
eou
s
• R
eti
nal
chan
ges
du
rin
g a
cti-
v
ati
on
- M
ore
tra
nsi
en
t co
nta
cts
in M
eta
I
-
Pre
fere
d o
rien
tati
on
sw
itch
es
up
on
iso
meri
zati
on
-
Reti
nal
elo
ng
ate
s in
Meta
I a
nd
M
eta
II
-
Reti
nal
dyn
am
ics
are
str
on
gly
co
up
led
to p
rote
in m
oti
on
s
• T
ran
siti
on
s in
volv
e p
rote
in's
m
ost
coll
ect
ive m
oti
on
s• H
6 o
rien
tati
on
an
d c
on
tact
s a
re e
nse
mb
le-d
ep
en
den
t• O
vera
ll s
low
rela
xati
on
tim
es
- E
ven
ts r
eq
uir
e h
un
dre
ds
of
ns
-
Mu
ltip
le s
imu
lati
on
s ess
en
tial
• T
ran
sien
t in
term
ed
iate
s• M
eta
I a
nd
Meta
II
are
in
eq
uil
ibri
um
-
On
ly M
eta
II
act
ivate
s G
pro
tein
• O
psi
n i
s ap
o f
orm
- C
ryst
al
looks
act
ive-l
ike
- E
xperi
men
tall
y h
as
min
imal
act
ivit
y
• D
ark
Op
sin
is
a p
rop
ose
d
i
nact
ive-l
ike, li
gan
d-f
ree
s
tate
• R
eti
nal
isom
eri
zes
from
11
-cis
to a
ll-t
ran
s w
hen
a p
hoto
n
i
s cap
ture
d b
y d
ark
-sta
te r
hod
op
sin
.
• T
o u
nd
ers
tan
d s
tate
-dep
en
den
t d
yn
am
ics
an
d t
heir
corr
ela
tion
wit
h r
eti
nal
moti
on
s w
e a
naly
zed
th
e f
oll
ow
ing
all
-ato
m M
D
sim
ula
tion
s:
• C
osi
ne o
f m
eth
yl o
rien
tati
on
wit
h
m
em
bra
ne n
orm
al
- M
eta
II
an
d D
ark
Rh
od
: re
tin
al
ori
en
-
t
ati
on
s d
isti
nct
ly p
ola
rize
d n
ear
C5
a
nd
C1
3
-
Meta
I:
more
hete
rog
en
eou
s co
nfo
r-
m
ati
on
s
• C
orr
ela
tion
betw
een
rh
od
op
sin
a
nd
reti
nal's
most
coll
ect
ive m
oti
on
s
- P
rin
cip
al
com
pon
en
t an
aly
sis
(PC
A)
-
Each
tra
ject
ory
of
eve
ry e
nse
mb
le f
or
lig
an
d a
nd
rece
pto
r
- A
lig
nm
en
t on
tra
nsm
em
bra
ne Cα
's• R
ep
rese
nta
tive
tim
e s
eri
es
of
PC
1
f
or
pro
tein
an
d r
eti
nal
• P
rote
in-r
eti
nal
corr
ela
tion
per
e
nse
mb
le
- C
om
pu
te P
CA
for
pro
tein
an
d r
eti
nal
for
each
tra
ject
ory
- C
orr
ela
tion
betw
een
PC
1 f
or
each
- A
vera
ge o
ver
6 t
raje
ctori
es
per
en
sem
ble
-
Diff
ere
nce
s are
not
stati
stic
all
y
s
ign
ifica
nt
(p-v
alu
e >
0.0
5)
-
Reti
nal
rem
ain
s st
ron
gly
cou
ple
d
• R
eti
nal-
pro
tein
in
tera
ctio
ns
-
Con
tact
: R
esi
du
e-r
eti
nal
cen
troid
-
t
o-c
en
troid
dis
tan
ce <
8 Å
-
Reti
nal
taken
as
a s
ing
le r
esi
du
e• I
lust
rati
on
: F
ive h
igh
est
o
ccu
pan
cy c
on
tact
s -
Ball
est
ero
s-W
ein
stein
nu
mb
eri
ng
in
su
pers
crip
t
• C
3-N
Z d
ista
nce
vs.
tim
e
- E
nse
mb
le a
vera
ge o
ver
6 t
raje
c-
t
ori
es
M
eta
I:
all
-tra
ns
• A
vera
ge h
eli
x 6
in
tera
ctio
ns
- C
on
tact
: C
en
troid
-to-c
en
troid
dis
tan
ce <
10
Å
- H
eli
x 6
taken
resi
du
e b
y re
sid
ue
Ab
str
act
Cla
ss A
GP
CR
Rh
od
op
sin
Reti
nal D
yn
am
ics D
isti
ng
uis
h P
rote
in S
tate
Sim
ula
tion
Deta
ils
Larg
e-S
cale
Pro
tein
Moti
on
s
Vary
Betw
een
En
sem
ble
s
Fu
ture
Dir
ecti
on
s
Reti
nal-
Pro
tein
Con
tacts
Con
clu
sio
ns
Reti
nal O
rien
tati
on
Vari
es w
ith
En
sem
ble
Reti
nal M
oti
on
s C
orr
ela
te w
ith
Overa
ll P
rote
in D
yn
am
ics
Helix 6
Dyn
am
ics C
hara
cte
rize
Rh
od
op
sin
En
sem
ble
s
En
sem
ble
-Avera
ge C
on
tacts
Dynam
ic L
igan
d-P
rote
in Inte
racti
ons
Alt
er
Rh
odopsi
n's
Con
form
ati
onal
Ense
mble
: Sim
ula
tions
of
Rhodopsi
n a
nd O
psi
nD
ynam
ic L
igan
d-P
rote
in Inte
racti
ons
Alt
er
Rh
odopsi
n's
Con
form
ati
onal
Ense
mble
: Sim
ula
tions
of
Rhodopsi
n a
nd O
psi
nLe
tty
Sala
s-Est
rad
a,
Nic
hola
s Le
ioatt
s, T
od
D.
Rom
o,
Shair
y A
zmy
Dania
l, A
lan G
rossfield
Univ
ers
ity
of
Roch
est
er
Med
ical S
chool, R
och
est
er,
NY,
US
ALe
tty
Sala
s-Est
rad
a,
Nic
hola
s Le
ioatt
s, T
od
D.
Rom
o,
Shair
y A
zmy
Dania
l, A
lan G
rossfield
Univ
ers
ity
of
Roch
est
er
Med
ical S
chool, R
och
est
er,
NY,
US
A
Rhod
op
sin P
hoto
cycl
e
Intr
ace
llula
r
Extr
ace
llula
r
(1) G
rossfi
eld
et
al.
, J.
Mol.
Bio
l. 2
00
8,
38
1:
47
8-4
86
T1
18
3.3
3G
12
13
.36
M2
07
5.4
2H
21
15
.46
F21
25
.47
W2
65
6.4
8Y2
68
6.5
1A
26
96
.52
Reti
nal
Dark
Rh
od
Meta
IM
eta
II
*:
p-v
alu
e v
s. M
eta
II
< 0
.05
0
0.2
0.4
0.6
0.81
|Correlation|
Dar
k R
hod
Met
a I
Met
a−II
Met
a II
Met
a I
Dar
k R
hod
Opsi
n
Dar
k O
psi
n
Dark
Rh
od
Dark
Op
sin
?
Op
sin
Meta
II
Meta
I
Bath
orh
od
op
sin
Lu
mir
hod
op
sin
all-
tran
sre
tinal
reti
nal ci
s-tr
ans
isom
eri
zati
on
11
-cis
reti
nal
photon
Ens
embl
eSt
ruct
ure
Sim
ulat
ion
Tim
e (µ
s)D
ark
Rho
d1U
196
runs
x1.
8M
eta
Ipr
evio
usw
ork(1
)6
runs
x6.
0M
eta
II3P
XO
6 ru
nsx
4.5
Ops
in3C
AP
6 ru
nsx
4.5
Dar
k O
psin
1U19
(liga
ndre
mov
ed)
6 ru
nsx
4.5
Tota
l≈
130
µs
C5
C9
C1
3
C5
C9
C1
3
Dat
a an
alys
is w
as p
erfo
rmed
usi
ng L
OO
S (L
ight
wei
ght
Obj
ect-
Orie
nted
Str
uctu
re li
brar
y),
an o
pen
sour
ce C
++
lib
rary
des
igne
d by
the
Gro
ssfie
ld l
ab.
LOO
S is
ada
ptab
le a
nd
com
patib
le w
ith a
ll m
ajor
sim
ulat
ion
pack
ages
, pro
vidi
ng a
leve
led
and
frien
dly
plat
form
fo
r dev
elop
ing
anal
ysis
app
licat
ions
. The
sou
rce
code
is a
vaila
ble
at:
http://loos.sourceforge.net
Reti
nal Elo
ng
ati
on
1212
.51313
.51414
.51515
.5
010
0020
0030
0040
0050
0060
00
Elongation (Å)
Tim
e (n
s)
Met
a I
Met
a II
Dar
k R
hod
• R
eti
nal
rap
idly
elo
ng
ate
s
aft
er
isom
eri
zati
on
Reti
nal
0
0.1
0.2 0
0.1
0.2
Population
0
0.1
0.2 −1
.0−0
.50.
00.
51.
0co
sΘ
Met
a I
Met
a II
Dar
k R
hod
12131416262728303132374041448693949798101
103
110
113
114
117
118
120
121
122
124
125
167
168
170
171
176
178
179
181
182
183
185
186
187
188
189
190
191
192
193
194
203
204
206
207
208
210
211
212
261
264
265
266
267
268
269
270
271
272
273
275
276
284
285
286
287
288
289
291
292
293
295 0
1000
2000
Retinal Contacts
Tim
e (n
s)
1111111112131416262728303132374041448693949798101
103
110
113
114
117
118
120
121
122
124
125
167
168
170
171
176
178
179
181
182
183
185
186
187
188
189
190
191
192
193
194
203
204
206
207
208
210
211
212
261
264
265
266
267
268
269
270
271
272
273
275
276
284
285
286
287
288
289
291
292
293
295 0
1000
2000
Retinal Contacts
Tim
e (n
s)
Dark
Rh
od
010
0020
0030
0040
0050
0060
00Ti
me
(ns)
Meta
I
010
0020
0030
0040
00Ti
me
(ns)
Meta
II
*:
p-v
alu
e v
s. D
ark
Rh
od
< 0
.05
htt
p:/
/tin
yurl
.com
/rtn
-rhod
-dyna
Post
er
PD
F
−1−0
.500.
51 −2−1012
050
010
0015
00Ti
me
(ns)
−1−0
.500.
51
Protein
−2−1012
050
010
0015
00
Retinal
Tim
e (n
s)
−1−0
.500.
51
Protein
−2−1012
050
010
0015
00
Retinal
Tim
e (n
s)
−1
−0.50
0.51
PC1 Displacement (Å)
010
0020
0030
0040
0050
0060
00Ti
me
(ns)
010
0020
0030
0040
00Ti
me
(ns)
Dark
Rh
od
Meta
IM
eta
II
−1.5−1
−0.50
0.51
1.52
010
0020
0030
0040
0050
0060
00
PC1 Displacement (Å)
Tim
e (n
s)
−2.5−2
−1.5−1
−0.50
0.51
1.5 −1
.5−1
−0.5
00.
51
1.5
2
PC2 Displacement (Å)
PC
1 D
ispl
acem
ent (
Å)
M1
N2
G3
T4
E5
G6
P7
N8
F9
Y1
0V
11
P1
2F
13
S1
4N
15
K1
6T
17
Y4
3I5
4L
57
T5
8V
61
T6
2Q
64
H6
5K
66
K6
7L
68
R6
9T
70
P7
1L
72
N7
3I7
5L
76
L7
9A
80
D8
3M
86
F9
1A
11
7T
11
8G
12
1E
12
2A
12
4L
12
5S
12
7L
12
8V
12
9L
13
1A
13
2E
13
4R
13
5Y
13
6V
13
8V
13
9C
14
0K
14
1M
14
3S
14
4N
14
5F
14
6R
14
7C
16
7P
17
0W
17
5S
17
6R
17
7Y
17
8E
18
1G
18
2M
18
3G
18
8I1
89
D1
90
Y1
91
Y1
92
T1
93
P1
94
H1
95
E1
96
E1
97
T1
98
N1
99
N2
00
E2
01
S2
02
F2
03
V2
04
I20
5Y
20
6M
20
7F
20
8V
20
9H
21
1F
21
2I2
13
I21
4P
21
5L
21
6I2
17
V2
18
I21
9F
22
0C
22
2Y
22
3G
22
4L
22
6V
22
7T
22
9V
23
0K
23
1E
23
2A
23
3A
23
4A
23
5Q
23
6Q
23
7Q
23
8E
23
9S
24
0A
24
1T
24
2T
24
3Q
24
4K
24
5H
27
8Q
27
9G
28
0S
28
1D
28
2F
28
3G
28
4P
28
5I2
86
F2
87
M2
88
T2
89
I29
0P
29
1A
29
2F
29
4A
29
5K
29
6T
29
7S
29
8A
29
9V
30
0Y
30
1N
30
2P
30
3V
30
4I3
05
Y3
06
I30
7M
30
8M
30
9N
31
0K
31
1Q
31
2F
31
3R
31
4N
31
5C
31
6M
31
7V
31
8T
31
9L
32
1C
32
2C
32
3K
32
5N
32
6 H6 Contacts
Dar
k R
hodM
eta
IM
eta-
IIO
psin
Dar
kO
psin
00.2
0.4
0.6
0.8
1
M1
N2
G3T4E5
G6
P7
N8F9Y
10V
11P
12F13
S14
N15
K16T1
7Y
43I54
L57
T58
V61T6
2Q
64H
65K
66K
67L68
R69T7
0P
71L72
N73I7
5L7
6L7
9A
80D
83M
86F91
A11
7T1
18G
121
E12
2A
124
L125
S12
7L1
28V
129
L131
A13
2E
134
R13
5Y
136
V13
8V
139
C14
0K
141
M14
3S
144
N14
5F1
46R
147
C16
7P
170
W17
5S
176
R17
7Y
178
E18
1G
182
M18
3G
188
I189
D19
0Y
191
Y19
2T1
93P
194
H19
5E
196
E19
7T1
98N
199
N20
0E
201
S20
2F2
03V
204
I205
Y20
6M
207
F208
V20
9H
211
F212
I213
I214
P21
5L2
16I2
17V
218
I219
F220
C22
2Y
223
G22
4L2
26V
227
T229
V23
0K
231
E23
2A
233
A23
4A
235
Q23
6Q
237
Q23
8E
239
S24
0A
241
T242
T243
Q24
4K
245
H27
8Q
279
G28
0S
281
D28
2F2
83G
284
P28
5I2
86F2
87M
288
T289
I290
P29
1A
292
F294
A29
5K
296
T297
S29
8A
299
V30
0Y
301
N30
2P
303
V30
4I3
05Y
306
I307
M30
8M
309
N31
0K
311
Q31
2F3
13R
314
N31
5C
316
M31
7V
318
T319
L321
C32
2C
323
K32
5N
326 H6 Contacts
Dar
k R
hodM
eta
IM
eta-
IIO
psin
Dar
k O
psin00.
2
0.4
0.6
0.8
1
M1
N2
G3T4E5
G6
P7
N8F9Y
10V
11P
12F13
S14
N15
K16T17
Y43I54
L57
T58
V61T62
Q64
H65
K66
K67L68
R69T70
P71L72
N73I75
L76
L79
A80
D83
M86F91
A11
7T1
18G
121
E12
2A
124
L125
S12
7L1
28V
129
L131
A13
2E
134
R13
5Y
136
V13
8V
139
C14
0K
141
M14
3S
144
N14
5F1
46R
147
C16
7P
170
W17
5S
176
R17
7Y
178
E18
1G
182
M18
3G
188
I189
D19
0Y
191
Y19
2T1
93P
194
H19
5E
196
E19
7T1
98N
199
N20
0E
201
S20
2F2
03V
204
I205
Y20
6M
207
F208
V20
9H
211
F212
I213
I214
P21
5L2
16I2
17V
218
I219
F220
C22
2Y
223
G22
4L2
26V
227
T229
V23
0K
231
E23
2A
233
A23
4A
235
Q23
6Q
237
Q23
8E
239
S24
0A
241
T242
T243
Q24
4K
245
H27
8Q
279
G28
0S
281
D28
2F2
83G
284
P28
5I2
86F2
87M
288
T289
I290
P29
1A
292
F294
A29
5K
296
T297
S29
8A
299
V30
0Y
301
N30
2P
303
V30
4I3
05Y
306
I307
M30
8M
309
N31
0K
311
Q31
2F3
13R
314
N31
5C
316
M31
7V
318
T319
L321
C32
2C
323
K32
5N
326 H6 Contacts
Dar
k R
hodM
eta
IM
eta-
IIO
psin
Dar
k O
psin00.
2
0.4
0.6
0.8
1
* * * ****
** **** * * * * * *
Met
a II
Met
a I
Dar
k R
hod
Opsi
n
Dar
k O
psi
n
0
0.1
0.2
0.3
0.4 0.
70.
80.
91
Population
cos
Θ
Dark
Rh
od
: 1
1-c
is
M
eta
II:
all
-tra
ns
12131416262728303132374041448693949798101
103
110
113
114
117
118
120
121
122
124
125
167
168
170
171
176
178
179
181
182
183
185
186
187
188
189
190
191
192
193
194
203
204
206
207
208
210
211
212
261
264
265
266
267
268
269
270
271
272
273
275
276
284
285
286
287
288
289
291
292
293
295
Residues Contacting Retinal
Dar
k R
hod
Met
a I
Met
a-II
00.2
0.4
0.6
0.8
1
12131416262728303132374041448693949798101
103
110
113
114
117
118
120
121
122
124
125
167
168
170
171
176
178
179
181
182
183
185
186
187
188
189
190
191
192
193
194
203
204
206
207
208
210
211
212
261
264
265
266
267
268
269
270
271
272
273
275
276
284
285
286
287
288
289
291
292
293
295
Residues Contacting Retinal
Dar
k R
hod
Met
a I
Met
a-II
00.2
0.4
0.6
0.8
1
M1
N2
G3T4E5
G6
P7
N8F9Y
10V
11P
12F13
S14
N15
K16T1
7Y
43I54
L57
T58
V61T6
2Q
64H
65K
66K
67L68
R69T7
0P
71L72
N73I7
5L7
6L7
9A
80D
83M
86F91
A11
7T1
18G
121
E12
2A
124
L125
S12
7L1
28V
129
L131
A13
2E
134
R13
5Y
136
V13
8V
139
C14
0K
141
M14
3S
144
N14
5F1
46R
147
C16
7P
170
W17
5S
176
R17
7Y
178
E18
1G
182
M18
3G
188
I189
D19
0Y
191
Y19
2T1
93P
194
H19
5E
196
E19
7T1
98N
199
N20
0E
201
S20
2F2
03V
204
I205
Y20
6M
207
F208
V20
9H
211
F212
I213
I214
P21
5L2
16I2
17V
218
I219
F220
C22
2Y
223
G22
4L2
26V
227
T229
V23
0K
231
E23
2A
233
A23
4A
235
Q23
6Q
237
Q23
8E
239
S24
0A
241
T242
T243
Q24
4K
245
H27
8Q
279
G28
0S
281
D28
2F2
83G
284
P28
5I2
86F2
87M
288
T289
I290
P29
1A
292
F294
A29
5K
296
T297
S29
8A
299
V30
0Y
301
N30
2P
303
V30
4I3
05Y
306
I307
M30
8M
309
N31
0K
311
Q31
2F3
13R
314
N31
5C
316
M31
7V
318
T319
L321
C32
2C
323
K32
5N
326
Residues Contacting Helix 6
Dar
k R
hodM
eta
IM
et-II
Ops
inD
ark
Ops
in00.2
0.4
0.6
0.8
1
M1
N2
G3T4E5
G6
P7
N8F9Y
10V
11P
12F13
S14
N15
K16T1
7Y
43I54
L57
T58
V61T6
2Q
64H
65K
66K
67L68
R69T7
0P
71L72
N73I7
5L7
6L7
9A
80D
83M
86F91
A11
7T1
18G
121
E12
2A
124
L125
S12
7L1
28V
129
L131
A13
2E
134
R13
5Y
136
V13
8V
139
C14
0K
141
M14
3S
144
N14
5F1
46R
147
C16
7P
170
W17
5S
176
R17
7Y
178
E18
1G
182
M18
3G
188
I189
D19
0Y
191
Y19
2T1
93P
194
H19
5E
196
E19
7T1
98N
199
N20
0E
201
S20
2F2
03V
204
I205
Y20
6M
207
F208
V20
9H
211
F212
I213
I214
P21
5L2
16I2
17V
218
I219
F220
C22
2Y
223
G22
4L2
26V
227
T229
V23
0K
231
E23
2A
233
A23
4A
235
Q23
6Q
237
Q23
8E
239
S24
0A
241
T242
T243
Q24
4K
245
H27
8Q
279
G28
0S
281
D28
2F2
83G
284
P28
5I2
86F2
87M
288
T289
I290
P29
1A
292
F294
A29
5K
296
T297
S29
8A
299
V30
0Y
301
N30
2P
303
V30
4I3
05Y
306
I307
M30
8M
309
N31
0K
311
Q31
2F3
13R
314
N31
5C
316
M31
7V
318
T319
L321
C32
2C
323
K32
5N
326
Residues Contacting Helix 6
Dar
k R
hodM
eta
IM
eta
IIO
psin
Dar
k O
psin00.
2
0.4
0.6
0.8
1
