Table S1. The sequence identities of human olfactory receptor OR1G1 (hOR1G1) with 13 available X-ray structures of G
protein-coupled receptors (GPCRs), turkey β1 adrenergic receptor (tβ1AR),[24] human β2 adrenergic receptor
(hβ2AR),[48] kappa opioid receptor (hOPRK),[37] rat M3 muscarinic receptor (rM3MR),[25] human
nociceptin/orphanin FQ receptor (hNOP),[49], human H1 histamine receptor (hH1HR),[50] mouse mu opioid
receptor (mOPRM),[51] human M2 muscarinic receptor (hM2MR),[26] mouse delta opioid receptor (mOPRD),[52]
human sphingosine 1-phosphate (hS1P1R),[36] human adenosine A2A receptor (hAA2AR),[27] bovine rhodopsin
(bRho),[31-35] and human D3 dopamine receptor (hD3DR).[28] In addition we include the overlaps for the most
accurate previously predicted structures: hM1MR,[53] Chemokine (C-C) motif receptor 1 (CCR1),[54] Serotonin
2C,[55]/ 2B[56], Urotensin II,[41] hA3AR,[57] hH3HR,[58]and CCR5. The sequence was ordered by the sequence
identity in all sequences. Each sequence identity of the transmembrane (TM) region was compared with hOR1G1.
GPCR
hOR1G1
All
100.0
TMs
100.0
TM1
100.0
TM2
100.0
TM3
100.0
TM4
100.0
TM5
100.0
TM6
100.0
TM7
100.0
tβ1AR
hβ2AR
hM1MR
hOPRK
hHT2C
hUT2R
18.5
17.3
15.7
15.7
15.3
14.7
22.7
21.9
18.3
16.5
19.9
19.8
33.3
25.9
25.9
22.2
25.9
22.2
21.4
28.6
17.9
28.6
28.6
32.1
26.9
26.9
19.2
19.2
19.2
26.9
14.7
14.7
5.9
5.9
8.8
17.7
15.6
9.4
12.5
18.8
12.5
6.3
25.0
21.4
25.0
3.6
17.9
7.1
21.7
26.1
21.7
17.4
26.1
26.1
hH3HR
rM3MR
hH1HR
hNOP
hCCR1
mOPRM
14.7
14.7
14.7
14.7
14.4
14.4
18.9
18.2
18.0
17.0
18.0
17.1
25.9
29.6
33.3
25.9
22.2
22.2
25.0
17.9
17.9
28.6
25.0
35.7
30.8
23.1
19.2
19.2
19.2
19.2
8.8
5.9
5.9
5.9
8.8
8.8
9.4
15.6
9.4
9.4
15.6
12.5
10.7
17.9
14.3
3.6
17.9
3.6
21.7
17.4
26.1
26.1
17.4
17.4
hM2MR
mOPRD
hS1P1R
hAA2AR
hHT2B
bRho
hD3DR
14.4
14.4
14.1
14.1
13.7
13.7
13.7
17.0
15.5
19.1
16.9
18.1
17.6
15.0
29.6
18.5
14.8
14.8
25.9
14.8
22.2
17.9
35.7
32.1
17.9
28.6
28.6
14.3
19.2
23.1
15.4
30.8
23.1
30.8
11.5
8.8
2.9
14.7
8.8
2.9
11.8
8.8
15.6
6.3
12.5
12.5
9.4
12.5
3.1
10.7
0.0
17.9
7.1
10.7
7.1
14.3
17.4
21.7
26.1
26.1
26.1
17.4
30.4
hCCR5
hAA3R
13.4
13.1
18.0
17.6
22.2
25.9
28.6
21.4
15.4
23.1
8.8
8.8
15.6
15.6
17.9
10.7
17.4
17.4
1
Table S2. Top 20 structures predicted for the human olfactory 1G1 receptors (hOR1G1) from the BiHelix analysis using
both (a) the fine sampling of η angles up to ±60° by 15° increment (60), leading to a total of (9)7 ~ 4.7 million
combinations or (b) with coarse sampling of η angles up to ±180° by 30° increment (360), leading to a total of (12)7
~ 35 million combinations with T6.50 vs. L6.50 alignment. All 2,000 models from CombiHelix were selected for
neutralization by their charge total energy (E) score (ChargeTot: kcal/mol) and were ordered by neutral interhelical
E (NiH: kcal/mol). The best E is shown in grey shading. The root mean square deviation (RMSD, Å) is with respect
to the all 0 structures.
rNiH
Source
H1
H2
H3
H4
H5
H6
H7
CInterH
CTotal
NInterH
NTotal
RMSD
1
tBeta1T.60
0
0
15
-15
-30
0
0
-420.56
789.61
-357.75
801.45
0.68
2
tBeta1T.360
0
0
0
0
-120
0
0
-400.74
867.81
-356.57
844.60
1.72
3
tBeta1T.60
0
0
15
-15
0
0
0
-402.47
828.45
-355.04
812.62
0.45
4
tBeta1T.360
0
0
30
120
-30
0
0
-417.43
870.10
-352.31
875.83
1.67
5
tBeta1T.60
0
-15
15
-15
0
60
60
-441.19
819.66
-351.74
822.29
1.47
6
tBeta1T.60
0
0
0
0
0
0
0
-396.47
858.02
-351.58
829.47
0.00
7
tBeta1T.60
0
0
15
-15
-30
0
15
-423.44
791.78
-350.74
812.14
0.71
8
tBeta1L.60
15
-15
15
-15
0
-15
45
-457.99
416.36
-350.10
459.57
0.91
9
tBeta1L.60
0
-15
0
0
15
-60
60
-425.65
326.90
-350.02
368.61
1.45
10
tBeta1T.60
0
0
0
0
-15
0
0
-407.64
824.17
-347.69
818.04
0.39
11
tBeta1T.60
0
-15
15
-15
60
0
0
-398.85
882.15
-346.88
845.08
1.11
12
tBeta1T.60
0
0
15
-15
0
15
0
-393.82
866.00
-346.54
845.13
0.53
13
tBeta1T.60
0
0
15
-15
60
0
0
-395.27
921.61
-346.12
910.51
1.07
14
tBeta1T.60
0
-15
0
-15
-30
0
0
-400.64
876.67
-346.03
857.18
0.68
15
tBeta1T.360
0
0
30
120
-150
0
0
-396.76
897.90
-344.63
876.58
2.47
16
tBeta1T.60
0
-15
15
-15
0
60
-60
-421.81
825.15
-344.19
816.59
1.48
17
tBeta1T.60
-15
-15
15
-15
0
0
0
-390.95
890.67
-344.16
848.51
0.57
18
tBeta1L.60
15
-15
0
0
15
-15
45
-423.61
388.79
-344.16
418.47
0.88
19
tBeta1T.60
0
0
15
-15
-15
0
0
-412.65
836.84
-343.90
844.89
0.52
20
tBeta1T.60
0
0
0
-15
-15
0
0
-403.59
861.81
-343.61
847.78
0.45
2
Table S3. Top 20 predicted structures of the human olfactory 1G1 receptors (hOR1G1) from the SuperBiHelix analysis with
a ±10° sampling of θ tilt angle and a ±30° sampling of both φ and η angles by 15° increments, leading to a total
of (3x5x5)7 ~ 1.7 trillion combinations. The structures were ordered by the average rank of charge interhelical,
charge total, neutral interhelical, and neutral total E (kcal/mol). The best E is shown in grey shading. Here the
best structure from Bihelix is now taken as = 0 ° for all 7 helices is shown in italics; it is now number 6.
Θ
φ
Η
RMSD
(Å)
#
H1 H2 H3 H4 H5 H6 H7 H1 H2 H3 H4 H5 H6 H7 H1 H2 H3 H4 H5 H6 H7
1
10
0
-10 10 -10 10 10 -30 -30 -30
0
0
30 15
0
-15
0
0
30
0
15
2.04
2
10
0
-10 10 -10 10 10 -30 -30 -30
0
15 30 15
0
-15
0
0
30
0
15
2.01
3
10
0
-10 10 -10 10 10 -30 -30 -30 -15 15 30 15
0
-15
0
15
30
0
15
2.08
4
10
0
-10 10 -10
0
0
-30 -30 -30
0
-15 30 30
0
-15
0
15
30
0
15
2.25
5
10
0
-10 10 -10
0
0
-30 -30 -30
0
-15 30 30
0
-15
0
0
30
0
15
2.25
6
0
0
0
0
0
0
0
0
0
0
0
0
0.00
7
10
0
-10 10 -10
0
0
-30 -30 -30 15 -15 30 30
0
-15
0
0
30
0
15
2.23
8
10
0
-10 10 -10
0
0
-30 -30 -15 -15 -15 30 30
0
-15
0
15
30
0
15
2.27
9
10
0
-10 10 -10
0
0
-15 -30 -15
0
-15 30 30
0
-15
0
0
30
0
15
1.91
10 10
0
-10 10 -10 10
0
-30 -30 -30
0
15 30
0
0
-15
0
0
30
0
0
2.09
11 10
0
-10 10 -10 10
0
-30 -30 -30
0
30 30
0
0
-15
0
0
30
0
0
2.08
12 10
0
-10 10 -10
0
0
-30 -30 -30 -15 -15 30 30
0
-15
0
0
30
0
15
2.31
13 10
0
-10 10 -10
0
0
-15 -30 -15
0
-15
0
0
30
0
15
1.88
14 10
0
-10 10 -10 10
0
-30 -30 -30 -15 15 30
0
0
-15
0
15
30
0
0
2.16
15 10
0
-10 10 -10 10 10 -30 -30 -30
0
15 30
0
0
-15
0
0
30
0
0
1.99
16 10
0
-10 10 -10 10 10 -30 -30 -30
0
15 30 15
0
-15
0
0
30
0
0
2.00
17 10
0
-10 10 -10 10 10 -30 -30 -30
0
30 30 15
0
-15
0
15
30
0
0
1.99
18 10
0
-10
-30 -30 -30
0
-15 30 30
0
-15
0
0
30
0
15
2.31
19 10
0
-10 10 -10 10 10 -30 -30 -30
0
30 30 15
0
-15
0
0
30
0
0
1.98
20 10
0
-10 10
0
15 30 30
0
-15
0
0
-30
0
0
2.22
0
0
0
0
-10
0
0
0
0
0
0
0
0
-30 -30 -15
0
0
0
0
3
0
30 30
Table S4. Top 24 predicted structures of the human olfactory 1G1 receptors (hOR1G1) from the SuperBiHelix analysis
sampling the translation of helix 6 (H6) with ±4 residues of hydrophobic center (HPC) by 2 residue increment
(247.7, 249.7, 251.7, 253.7, 255.7) in addition to the standard sampling, a ±10° sampling of θ tilt angles, a ±30°
sampling of both φ and η angles by 15° increments. The structures were ordered by the average rank of charge
interhelical, charge total, neutral interhelical, and neutral total E (kcal/mol). The case with  = 0 ° for all 7
helices (the best structure from SuperBiHelix) with the H6 HPC of 251.7 in italic is ranked by top 24 and the
best E is shown in grey shadings.
Θ
Φ
Η
#
H1 H2 H3 H4 H5 H6 H7 H1 H2 H3 H4 H5 H6 H7 H1 H2 H3 H4 H5 H6 H7
HPC RMSD
(Å)
H6
1
10
0
2
10
0
3
10
0
-10 10 -10
4
10
0
-10 10
5
10
0
6
10
7
0
-30 -30 -30
0
0
-15
0
0
30 15
0
249.7
2.59
0
-15 -15 -30 15
30 15
0
0
0
0
0
15
0
249.7
2.22
0
0
-30 -30 -15
-30 30 30
0
-15
0
0
-15 30
15
249.7
2.69
0
0
0
-30 -30 -15 -15 -30 30 30
0
-15
0
0
-30 30
15
249.7
2.89
-10 10
0
0
0
-30 -30 -15
0
-30 30 30
0
-15
0
0
-30 30
15
249.7
2.85
0
-10 10
0
0
0
-30 -30 -15
0
-15 30 30
0
-15
0
0
30 30
15
249.7
2.74
10
0
-10 10 -10 10
0
-30 -30 -30
0
30
0
0
-15
0
0
0
15
0
249.7
2.56
8
10
0
-10 10 -10 10
0
-30 -30 -30 -15 15 30
0
0
-15
0
15
30 15
0
249.7
2.64
9
10
0
-10 10
0
0
-30 -30 -15
-30 15 30
0
-15
0
0
-30 30
15
247.7
3.45
10 10
0
-10 10 -10 10
0
-30 -30 -30 -15 15 30
0
0
-15
0
0
30 15
0
249.7
2.63
11 10
0
-10 10
0
0
0
-30 -30 -15 -15 -15 30 30
0
-15
0
0
30 30
15
249.7
2.78
-10 -10 10
0
0
15 -30
0
0
30 30 -30
247.7
3.37
0
0
-15
0
0
-30 30
15
249.7
2.71
12
0
-10 10 -10 10
0
0
-10 10
0
-10 -30 -15
0
0
0
0
15 30
0
0
-15 -30
30
13 10
0
-10 10
0
0
-30 -30 -15
0
14 10
0
-10 10 -10 10
0
-30 -30 -15
0
-15 15
0
0
-15
0
0
30 30
0
247.7
3.31
15 10
0
-10 10
0
0
0
-30 -30 -15
0
-15 30 30
0
-15
0
0
30 15
15
249.7
2.70
16 10
0
-10 10
0
0
0
-30 -30 -15
0
0
30 30
0
-15
0
0
30 30
15
249.7
2.69
17 10
0
-10 10
0
-30 -15 -30
0
0
30 15
0
0
0
0
0
0
249.7
2.55
0
15 -30
0
0
15 30 -30
247.7
3.34
0
-15
0
0
30 30
0
247.7
3.37
0
0
0
0
15
0
249.7
2.24
18
0
0
0
-10 -10 10
19 10
0
20 10
0
21 10
0
0
0
-15 -30
30
-10 10
0
-15 -15 -30 30
0
-10 10 -10 10
0
-30 -30 -15
0
-30 15 -30
0
-15
0
0
30 30
15
247.7
3.45
22 10
0
-10 10 -10 10
0
-30 -30 -15
0
30 15
0
0
-15
0
0
30 30
0
247.7
3.28
23 10
0
-10 10 -10 10
0
-30 -30 -15
0
-30 15
0
0
-15
0
0
30 30
0
247.7
3.34
24
0
0
0
0
0
0
0
0
251.7
0.00
0
0
0
0
0
0
0
0
0
0
-30 15 -15
15
-30 -30 -15
0
0
30 30
0
0
-10 10 -10 10
-10 -30 -15
0
0
0
0
4
30 15 -15
0
0
Table S5. Scoring energy of the n-nonanal bound to the human olfactory 1G1 receptor (hOR1G1). Conf. # (Conformation
number is from the conformational search. UCav (Unified cavity) energy is the sum of van der Waals (vdW),
Coulomb, and H-bond energy (kcal/mol) in the unified cavity and BE (binding energy) is calculated by Complex
energy- protein energy – ligand energy. The unit of energy is kcal/mol.
#
Protein Conf. #
Nonanal Conf. #
UCav
BE
1
Top24
Conf1
-24.69
-30.17
2
Top1
Conf1
-23.01
-24.11
3
Top18
Conf1
-22.23
-26.08
4
Top18
Conf0
-21.41
-24.94
5
Top24
Conf0
-21.27
-31.02
6
Top24
Conf89
-21.24
-23.59
7
Top18
Conf0
-21.23
-28.19
8
Top24
Conf1
-21.19
-23.25
9
Top12
Conf1
-20.95
-28.60
10
Top24
Conf0
-20.77
-29.83
5
Table S6. The final changes from the beginning to the end of x, y, HPC, θ, φ, and η of each 7 transmembrane (TM) helix of
the human olfactory 1G1 receptors (hOR1G1) during 40ns molecular dynamics.
X
Y
HPC
φ
η
1
-0.9
-4.4
-0.5
1.9
-10.8
-72.1
2
0.5
0.0
-0.9
4.8
-5.5
-34.9
3
0.0
0.0
-0.7
-1.3
-14.8
-24.2
4
1.0
4.4
-0.1
-7.7
4.5
-6.8
5
-4.1
3.9
0.4
10.1
-4.2
-13.1
6
-5.3
1.7
0.9
7.2
-19.7
-59.0
7
-0.8
0.4
0.3
-0.9
-1.8
-13.8
AVE
-1.4
0.9
-0.1
2.0
-7.5
-32.0
TM#
6
θ
P47890|OR1G1-1
Q8NGR6|OR1B1-1
Q8NGL4|OR5DD-2
Q8NGL9|OR4CG-3
Q8NGT5|OR9A2-4
Q8NHA4|O2AE1-5
Q5JRS4|O10J3-6
Q9H342|O51J1-7
M
-
M
-
M
-
M
A
W
M
-
E
S
Q
P
-
M
K
P47890|OR1G1-1
Q8NGR6|OR1B1-1
Q8NGL4|OR5DD-2
Q8NGL9|OR4CG-3
Q8NGT5|OR9A2-4
Q8NHA4|O2AE1-5
Q5JRS4|O10J3-6
Q9H342|O51J1-7
M
I
V
L
F
V
L
I
Y
Y
Y
Y
Y
F
Y
Y
L
L
T
L
L
L
L
I
V
T
V
G
V
I
L
I
T
T
T
T
T
A
T
I
V
I
V
L
L
V
L
F
A G
L G
V G
L G
MG
S G
S G
L G
- - - - - - - S N
1.50
N L
N V
N L
N L
N T
N T
N V
N G
P47890|OR1G1-1
Q8NGR6|OR1B1-1
Q8NGL4|OR5DD-2
Q8NGL9|OR4CG-3
Q8NGT5|OR9A2-4
Q8NHA4|O2AE1-5
Q5JRS4|O10J3-6
Q9H342|O51J1-7
N
H
N
D
G
N
G
I
I
L
L
A
L
Y
L
F
Q
V
V
L
L
L
L
L
I
S
V
L
F
S
N
F
Q
H
E
K
L
G
P
G
S
Y
Y
K
G
K
H
N
Q
P
R
T
C
K
Q
T
R
-
A
T
T
T
Q
S
P
E
P47890|OR1G1-1
Q8NGR6|OR1B1-1
Q8NGL4|OR5DD-2
Q8NGL9|OR4CG-3
Q8NGT5|OR9A2-4
Q8NHA4|O2AE1-5
Q5JRS4|O10J3-6
Q9H342|O51J1-7
H
S
Y
P
D
T
A
Q
P47890|OR1G1-1
Q8NGR6|OR1B1-1
Q8NGL4|OR5DD-2
Q8NGL9|OR4CG-3
Q8NGT5|OR9A2-4
Q8NHA4|O2AE1-5
Q5JRS4|O10J3-6
Q9H342|O51J1-7
A
G
E
G
K
G
D
-
N
D
S
P
S
P
A
-
G
-
H
N
T
N
N
R
F
-
V
-
P47890|OR1G1-1
Q8NGR6|OR1B1-1
Q8NGL4|OR5DD-2
Q8NGL9|OR4CG-3
Q8NGT5|OR9A2-4
Q8NHA4|O2AE1-5
Q5JRS4|O10J3-6
Q9H342|O51J1-7
I
L
T
F
V
T
I
I
S
S
S
S
S
S
S
S
- A G
- - - - - - 5.58
Y T
Y V
Y M
Y V
Y T
Y V
Y V
Y G
P47890|OR1G1-1
Q8NGR6|OR1B1-1
Q8NGL4|OR5DD-2
Q8NGL9|OR4CG-3
Q8NGT5|OR9A2-4
Q8NHA4|O2AE1-5
Q5JRS4|O10J3-6
Q9H342|O51J1-7
S
F
P
T
Q
S
S
-
T
Q
K
V
T
Q
Q
H
H
N
T
F
Q
C
S
R
N V
R I
L I
I F
Y I
F I
L I
L I
TM7
A Q
Q Y
S L
MV E
L L
L G
S P
S
S
S
P
G
T
S
V
I
N
M
N
K
N
-
L
S
Q
N
S
-
T
F
S
M
Q
T
-
A
M
M
-
P
Q
D
-
N
L
N
L
A
N
H
G
V I
L I
I I
S V
I V
L I
I I
V I
3.25
C L
C L
C I
C M
L S
C A
C A
C L
I
S
R
K
C
C
R
R
T
W
L
T
V
I
L
T
D
D
N
S
D
D
D
D
T
S
S
Q
K
P
H
I
Q
R
K
A
R
Q
H
A
Y
F
C
F
S
F
F
V
F
F
F
S
L
L
F
L
G
L Q L
A Q F
MQ F
I Q V
L H V
T Q H
T Q L
F P D
TM4
- L HY I L I MS P
- L HY A L V MN H
- L L Y T T I MS Q
- L H Y MT I I S Q
- L R Y NI I MN S
- L R Y A V L MN K
- L R Y S V I MG K
L WHR S Y Y R T E
L H
L H
L H
L K
L Q
L H
L H
L H
3.32
F ML
F Y A
A C I
S H V
N F S
Y L C
Y L T
H P F
G L
Q R
K L
WV
S T
K V
R A
K H
C
C
C
C
C
G
C
Y
I
A
A
G
I
L
I
A
F L
C L
L L
V L
WV
MM
Q L
H G
V
L
V
M
V
A
A
S
E
N
F
V
S
K
V
-
I
L
I
I
L
V
I
-
P
P
N
N
D
Y
S
-
H
H
N
H
H
H
H
-
C
C
C
C
C
C
C
L
D
D
D
D
D
E
D
L
I
H
H
L
R
F
V
S
N
R
S
Q
G
P
R
A
L
L
V
L
L
V
L
S
S
R
S
K
K
K
K
Y
L
A
A
Q
L
L
L
L
S
S
S
A
S
V
A
S
C
C
Y
C
C
C
C
C
T
S
S
S
D
G
T
G
D
D
D
E
N
D
D
N
F
G
F
L
I
L
I
L
S
A
T
H
S
Q
S
H
T
A
T
S
T
S
T
T
I
I
I
I
V
I
V
L K I P
L RL P
M K MR
L RN H
L K I P
I QMR
L K I A
L GI A
S
S
S
S
S
S
S
T
A
A
A
A
A
S
A
G
Q
A
S
E
S
G
E
E
P L
P L
V I
P L
Q L
A V
H L
P Q
TM6
G K
G R
G R
V I
G R
S K
G Q
G R
R
R
Q
K
R
R
K
K
K
R
K
K
K
N
K
K
A
A
T
A
A
A
A
A
F
V
F
L
F
F
F
L
S
S
S
S
S
A
A
N
K
Q
I
Y
Q
Q
L
L
D
D
V
D
N
N
D
Q
T V AS
MV AS
T V AS
K MI A
K I VS
K V GS
R L I S
A M MA
M
M
F
F
L
F
T
A
Y
Y
Y
Y
V
Y
Y
Y
T
T
T
T
S
S
T
L
V
A
V
V
V
I
H
F
T
T
I
T
T
T
S
P
P
P
P
S
P
P
P
P
ML
L A
ML
F L
F L
T L
T E
V V
N
N
N
N
N
N
P
N
T C
T C
T C
T C
T F
T C
T C
T C
7.50
P F
P F
P L
P V
P F
S L
C C
P I
I
I
I
I
Y
I
I
I
N
S
G
E
K
-
K
R
L
-
L I I L
T L V L
G MI I
L I I I
V I I V
L T I L
I I MT
I I L H
TM3
S Y S G
P AA R
S F S G
S F S E
- - - S F V G
A T QS
S L E A
F
F
F
C
F
F
F
-
F
F
I
F
Y
Y
F
-
V
V
V
V
L
V
V
N
M
-
V
I
A
G
L
I
H
F
S
S
S
N
S
T
F
F
- I
H S
- T
N V
S A
S L
- V
L P
TM2
T P
S P
T I
N P
S P
T P
T P
Q P
S
P
P
T
T
A
T
T
E
V
T
E
E
D
E
T
C
F
F
F
F
F
F
F
M
M
M
M
M
M
M
M
Y
Y
C
F
Y
Y
Y
Y
F
Y
F
F
F
F
F
L
F
F
F
F
C
L
F
F
V
G
G
G
G
G
G
I
F
F
F
V
F
Y
F
I
I
F
I
S
L
I
V
F
L
F
I
L
I
L
I
A
I
V
I
V
V
V
Q
I
I
V
I
I
I
I
V
V
N
N
N
N
N
N
Q
T
F
F
F
L
F
L
F
I
HS
HT
C S
HS
S E
NS
MA
L L
L
V
L
L
T
L
I
L
R
H
R
K
R
R
E
K
G
G
G
G
G
G
G
G
L
L
V
V
L
V
G
A
F L A N L S
L L R G L S
F L S H L S
F L F Y L S
F L S H L S
L L S QL S
F L C ML S
F L A ML A
3.39
ML E A F L L A
V T D T L V I A
V T E T F ML A
C L E I F I L I
T ME F A L L G
G A E C F L L A
I NN C F L L T
H DG AS C AA
4.50
S A S WI M N A
A L S WV V S I
A G S Y T WG I
A V A WV G S C
I V S WV F G F
V M S WL G A S
S GS L G I GL
V A H S L MA S
TM5
P F T NE L VI
I H S NE L AI
P Y I S QR L C
T Y V VN L L L
T L L T E F I L
I T V Y E T T V
T T V NE I I N
I S V NN I Y G
6.40
S S H L S V VS
G S H L T MV G
A S H L T A I T
V S H I I V VI
A S H F T C VV
G S H L T V VS
A S H L T V VI
G S H VC A VL
L
L
L
L
L
L
E
I
L
L
L
L
L
E
E
V
V
V
A
L
V
V
V
G
E
R
E
Q
G
D
S
G
S
S
S
T
T
T
P
S
L
L
L
L
L
L
F
L
TM1
Q L E E Q
A N I S Y
Y P E I Q
D P F W K
S Q G L H
D S L T H
R R Q H K
- E S E H
2.50
AD A C F V
I D MG L S
T D F C F S
S D T C L S
L E I L V T
MD L M H V
S E T C Y T
AE V R V S
3.50
MA Y D C Y
MA L D R Y
MA Y D R F
T A V D R Y
MA V D R Y
MS Y D R Y
MG Y D R Y
HV F G P L
S
S
S
T
P
F
S
P
Y
Y
Y
Y
F
Y
Q
Y
F
L
I
I
H
I
L
I
QE
K D
K D
T E
DK
K D
GG
K E
F
L
L L H
ML R
L I L
L V Q
I WP
L I H
I V Q
WP Q
K
T
V
K
H
L
L
L
P
L
P
I
I
F
V
W
L
L
L
V
L
L
F
I
F
F
F
F
F
F
F
S
G
F
L
V
A
S
V
V
S
L
V
I
I
L
V
P
S
T
T
T
T
S
V
A
T
V
V
S
I
T
A
S
T
T
V
I
I
I
I
T
V
L
T
T
V
I
I
L
P
P
P
P
P
L
P
P
K ML
QL L
K L L
R MI
M ML
K MA
H ML
T VL
A
A
E
V
W
T
S
G
V
V
V
V
V
V
V
Y
A
A
A
D
A
A
A
S
I
I
V
I
V
I
I
H
C
C
C
C
C
C
C
L
H
D
K
K
N
H
N
Q
P
P
P
P
P
P
P
P
T
E
L
T L
V G
T Y
I F
I Y
MA
V T
C P
L
L
F
L
A
I
S
L
S
C
S
P
T
P
P
-
F
W
F
F
F
F
F
-
C
T
C
C
R
C
C
-
CL
L I
I I
ML
P T
L I
L V
L I
I
V
L
I
I
S
F
V
T
L
N
I
I
L
V
T
G L
ML
E V
C A
L I
L L
L V
F G
F F
L Y
F H
F F
GY
WF
HY
Y Y
G
G
G
G
G
G
G
V
G L
G F
I F
G A
V F
I V C
T S
6.50
T S
T I
T I
P C
S C
A C
C A
P M
MN S L
V L P L
L L D L
A L S L
T F Q F
L MH F
V F G L
T F - 5.50
I C V L
G P C A
S S L I
V S Y V
G S L I
L P I F
L P MG
L DS L
F
I
L
I
L
I
S
I
C
C
F
F
F
F
I
G
D
Y
Y
Y
Y
Y
Y
S
K S
K G
NN
K S
K E
AK
RC
HG
S L R
A L C
MF E
A MR
A L R
A L R
S A Q
A I V
K
R
K
K
D
R
S
R
L I
L L
L V
L W
G M
V L
R G
ML
T G
E G
I A
N S
MA
S S
V S
I V
V
V
L
M
L
S
I
L
F
F
F
F
F
T
F
F
L
L
L
L
F
M
L
S
F
A
F
R
F
V
T
L
F S
F Q
C V
T C
V K
MR
L K
I V
S
P
P
L
P
P
P
H
R
L
P
P
N
A
K
R
K
G
WV R
E WV
V T K
S K K
K R C
R R D
A K N
L E K
K
K
L
L
C
V
S
R
I H
VD
I I T
QL
I T
VS
RR
S
P
D
L
Q
L
V
Fig. S1. The multiple sequence alignment of family heads of 7 clusters for 398 human olfactory receptors.
7
A
B
C
W4.50 D2.50
N2.45
W4.50 D2.50
S2.45
N1.50
N7.49
N7.49
W4.50 D2.50
N2.45
N1.50
N7.49
N1.50
D3.49
R3.50
K6.30
R3.50
E6.30
D
N6.30
F
E
W4.50
N2.64
W4.50 D2.50
D2.50
N2.45
N2.45
N7.49
N1.50
N7.49
R3.50
L6.30
N1.50
D3.49
R3.50
E6.30
Fig. S2. A) Predicted best structures of human olfactory 1G1 receptor (hOR1G1) from SuperBiHelix analysis, B) the X-ray
structures of turkey β1 adrenergic receptor (tβ1AR),[24] C) human sphingosine 1-phosphate (hS1P1R),[36] D) kappa
opioid receptor (hOPRK),[37] E) bovine rhodopsin (bRho),[31-35] and F) superimposition of all five structures (A
to E)
8
B
A
C169-C179
C97-C189
Helix formation
C97-C189
Fig. S3. Result of 10 cycles of simulated annealing (50 K to 600K) A) one conserved disulfide constraint between C97C189, B) two disulfide constraints between C97-C189 and between C169 and C179 in the second extracellular loop.
We found that an α-helix was formed in EC2 from D180 to T190 after just 8 cycles of annealing. The bottom graph
shows the total energy at each cycle.
9
Fig. S4 Trajectory analysis of x, y, HPC, θ, φ, and η of each 7 transmembrane (TM) helix of the human olfactory 1G1
receptors (hOR1G1) during 20ns molecular dynamics.
10
Fig. S5 Transmembrane (TM) region of the human olfactory 1G1 receptor. Each TM region was extended by capping rules
and the secondary structure prediction, PORTER[30] and SSPro[22] from raw region from the hydrophobicity
profile. The capped regions are shown as in the raw of CAP. The hydrophobic center (HPC) which is the middle
residue in the raw TM region (RawMid) is shown as *.
11