In Silico Investigation of Interactions Between Human Cannabinoid Receptor-1 and Its
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Supporting Information
In Silico Investigation of Interactions between Human
Cannabinoid Receptor-1 and Its Antagonists
Guanglin Kuang, Guoping Hu, Xianqiang Sun, Weihua Li, Guixia Liu, Yun Tang*
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China
University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
*Corresponding Author. Tel.: +86-21-6425-1052; Fax: +86-21-6425-3651; E-mail:
1 Supporting Materials
Figure S1. Superimposition of the modeled structure of human CB1 receptor with the
template structure of human β2-adrenergic receptor (PDB ID:2RH1, white). This figure was prepared with PyMol (http://www.pymol.org/).
Figure S2. Ramachandran plot of the CB1 homology model.
Figure S3. Detailed interactions between SLV 319 and the homology model of CB1 receptor. The ligand is shown in ball-and-stick mode and residues in stick mode. The carbon atoms of the ligand are green and those of the receptor in gray. The hydrogen bond is presented as red lines. Only polar hydrogen atoms are displayed for clarity.
Figure S4. Correlation between experimental and predicted activities of compounds in the test set used by Weber et al , compared with the original results.
Table S1. The structures, experimental and predicted binding affinities (Ki) of compounds in the test set.
Table S2. Structures, experimental and predicted activities of compounds used by
Weber et al .
2 Figure S1. Superimposition of the modeled structure of human CB1 receptor with the
template structure of human β2-adrenergic receptor (PDB ID:2RH1, white). This figure was prepared with PyMol (http://www.pymol.org/).
3 Figure S2. Ramachandran plot of the CB1 homology model.
4 Figure S3. Detailed interactions between SLV 319 and the homology model of CB1 receptor. The ligand is shown in ball-and-stick mode and residues in stick mode. The carbon atoms of the ligand are green and those of the receptor in gray. The hydrogen bond is presented as red lines. Only polar hydrogen atoms are displayed for clarity.
5 Figure S4. Correlation between experimental and predicted activities of compounds in the test set used by Weber et al , compared with the original results.
6 Table S1. The structures, experimental and predicted binding affinities (Ki) of compounds in the test set.
Compound Structure Experimental Predicted Errorb Reference
No. Ki (nM)a Ki (nM) Ts1 351 460 1.3
O N N H
N N Cl
Ts2 39 10 -3.9 O N N H
N N Cl
Cl Ts3 273 590 2.2 O N N H
N N
Cl Ts4 20 41 2.1
N N O
N N Cl Cl
Ts5 21 4.4 -4.8
N N O
N N Cl Cl
Ts6 5 4.1 -1.2
N N O
N N Cl Cl
Ts7 F 0.3 3.8 12.7 F N F N O
N N Cl Cl
7 Ts8 28 230 8.2 N N O Cl
N N
Cl
Ts9 F 1 4.1 4.1 F N F N O
N N Cl Cl
F Ts10 F 1 3.8 3.8 N F N O
N N Cl Cl
Ts11 110 57 -1.9
N N O N
Ts12 178 130 -1.4 N N O
N
Ts13 O 631 78 -8.1 HN N O N
Ts14 25 49 2.0 N HN N O N
Ts15 203 100 -2.0
O
HN N O N
Ts16 650 640 -1.0
N O
N NH2
8 Ts17 2200 180 -12.2 N N N O
NO2
Ts18 HN 2381 230 -10.4 N O
N
Ts19 195 59 -3.3
HN N O N
Ts20 509 130 -3.9 HN N O
N
Ts21 O 16 6.2 -2.6
N
N Cl
Cl
Ts22 O 10 9.8 -1.0
N
N Cl
Cl
Ts23 O 200 100 -2.0
N
N Cl Cl Cl
Ts24 20 130 6.5 O N N
N Cl O
Ts25 O 74 83 1.1 N N
N
O
9 Ts26 O 7.5 8.8 1.2
N
N Cl Cl
Cl
Ts27 O 308 170 -1.8
O O N N N N H
Ts28 O 325 120 -2.7 S O
O NH
H N S O O
Ts29 520 400 -1.3 O O Cl N N
O
Ts30 F 611 610 -1.0 O
N H O O S N
Ts31 875 610 -1.4 S N N O O O
F
Ts32 F 1030 2700 2.6
O O N N N
Ts33 1177 870 -1.4 O N N
N NO2 NH
F Ts34 F F 2314 1400 -1.7
N O
N S N N
O
10 Ts35 O 2396 210 -11.4
N
HN O O
N
Ts36 S 1000 1100 1.1
O O N S N N F S F F N
Ts37 92 2400 26.1 O S N O O
N O
Ts38 O 227 13 -17.5 O N O N
N N
Cl Ts39 264 310 1.2 N
O N
S
O N H O Ts40 F 273 160 -1.7 N
N Br O O
Ts41 O 494 470 -1.1 N N H N N Cl
Ts42 O 264 370 1.4 N N H N N Cl
11 Ts43 14 41 2.9 Cl O N N H OH N
Cl Ts44 12 34 2.8
O N Cl H N
N N Cl
Cl
Ts45 40 12 -3.3 O N N H N N
Cl Ts46 25 11 -2.3 O N N H N N Cl Cl
Cl Ts47 18 14 -1.3 O
N H N N Cl Cl
Cl Ts48 26 8.3 -3.1 O N N H N N Cl
Cl Ts49 72 6 -12.0 O
N H N N Cl
Cl Ts50 Br 70.3 120 1.7
O O N N N H Br O Ts51 O 243.8 660 2.7
N N O
12 Ts52 Cl 6.1 39 6.4 N N N N N
Cl Cl H Ts53 N 61 42 -1.5 O
N N Cl Cl
Ts54 4.7 41 8.7 N O
N N Cl Cl
Ts55 2.5 6.4 2.6 N O
N N Cl Cl
Ts56 24 41 1.7
N O
N N Cl Cl
Ts57 F 0.7 4.9 7.0 F
N O
N N Cl Cl
Ts58 NH 83 49 -1.7 O O
N Cl N
Cl
Ts59 F 1 5.9 5.9 F F
N O O
N Cl N
Cl
13 Ts60 F F 0.6 4.4 7.3 F N N O
N N Cl Cl
a Ki values were all determined on human CB1 receptor. b The Error column shows the ratio of predicted activity to measured activity (or the ratio of measured activity to predicted activity, if that gives a number greater than 1, in which case the number is negative).
14 Table S2. Structures, experimental and predicted activities of compounds used by
Weber et al .
Cpd Structure pIC50 Experimental Predicted by HQSAR CoMFA Pharmacophore
1 Cl 6.32 6.07 7.23 6.52
HN N Cl N O Cl 2 Cl 7.19 6.39 7.63 7.12
HN Cl N O Cl 3 Cl 7.28 7.08 7.56 7.49
H N N O Cl Cl 4 Cl 7.46 7.59 6.60 7.57
H N N O Cl Cl Cl 5 O 7.49 7.75 7.65 8.24
H2N
O N
Cl Cl Cl 6 O 7.74 7.96 8.01 7.57
NH2
N O
Cl Cl 7 Cl 8.22 8.00 7.72 7.66
Cl
H Cl N N
O O
Cl 8 O 8.54 8.80 7.91 8.52
O
N O
Cl Cl
15 Cl 9 O 8.72 8.11 8.16 8.16
O
O N
Cl Cl
10 F 8.82 8.83 9.05 8.52
Cl HN
O F N O
Cl Cl F 11 F 8.14 8.20 7.87 8.11 N
F N O
Cl Cl F
12 Cl 8.47 9.41 8.46 8.03 N
O N F Cl Cl F F
16 References
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