[Supporting Information]
Identification of dual Acetyl-CoA carboxylases 1 and 2 inhibitors by pharmacophore based virtual screening and molecular docking approach
Anuseema Bhadauriya,a,b Gaurao V. Dhoke,a,b Rahul P. Gangwal,a Mangesh V. Damre,a Abhay T. Sangamwara,*
aDepartment of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sect-67, S.A.S. Nagar, Punjab-160 062, India
bAuthors have equal contribution
*Corresponding author: Tel: 0172-2214682
E-mail:
S. No. / Content / Page No.1 / Experimental and predicted IC50 values of ACC1 training set molecules / S2
2 / Chemical structures of ACC1 training set compounds and their IC50 values (nM) in parentheses / S3
3 / Experimental and predicted IC50 values of ACC2 training set molecules / S4
4 / Chemical structures of ACC2 training set compounds and their IC50 values (nM) in parentheses / S5
5 / Experimental and predicted IC50 values of ACC1 inhibitors in the test set / S6
6 / Chemical structures and IC50 value of ACC1 test set compounds / S8
7 / Experimental and predicted IC50 values of ACC2 inhibitors in the test set / S12
8 / Chemical structures and IC50 value of test set compounds for ACC2 inhibitors / S14
9 / Chemical features of best ACC1 pharmacophore hypothesis (Hypo1_ACC1) with their inter-feature distance constraints in angstrom (Å) / S18
10 / Chemical features of best ACC2 pharmacophore hypothesis (Hypo1_ACC2) with their inter-feature distance constraints in angstrom (Å) / S18
11 / The difference in the cost value of hypotheses between the initial spread sheet and 19 random spread sheets generated after CatScramble run (Fischer randomization test) for ACC1inhibitors / S19
12 / The difference in the cost value of hypotheses between the initial spread sheet and 19 random spread sheets after CatScramble run (Fischer randomization test) for ACC2 inhibitors / S19
13 / Chemical structures of top three hits obtained through sequential virtual screening process / S20
Table S1 Experimental and predicted IC50 values of ACC1 training set molecules
Compound / FitValue / Exp. IC50 (nM) / Pred. IC50 (nM) / Errora / Exp. scaleb / Pred. scaleb1 / 7.02 / 7.4 / 11.43 / +1.54 / +++ / +++
2 / 6.96 / 17 / 13.11 / -1.29 / +++ / +++
3 / 6.26 / 31 / 65.89 / +2.12 / +++ / +++
4 / 6.21 / 60 / 75.16 / +1.25 / +++ / +++
5 / 6.09 / 69 / 97.68 / +1.41 / +++ / +++
6 / 5.79 / 140 / 194.11 / +1.38 / +++ / +++
7 / 6.13 / 154 / 90.40 / -1.70 / +++ / +++
8 / 5.45 / 340 / 432.54 / +1.27 / ++ / ++
9 / 5.53 / 415 / 354.18 / -1.17 / ++ / ++
10 / 5.76 / 470 / 212.47 / -2.21 / ++ / ++
11 / 5.00 / 750 / 1,215.26 / +1.62 / ++ / ++
12 / 4.73 / 975 / 2,266.74 / +2.32 / ++ / +
13 / 4.81 / 1,000 / 1,876.49 / +1.87 / ++ / ++
14 / 5.35 / 1,100 / 540.68 / -2.03 / ++ / ++
15 / 5.38 / 1,300 / 504.29 / -2.57 / ++ / ++
16 / 4.62 / 1,780 / 2,870.52 / +1.61 / ++ / +
17 / 4.93 / 2,530 / 1,429.91 / -1.76 / + / ++
18 / 4.50 / 2,770 / 3,791.13 / +1.36 / + / +
19 / 4.61 / 3,000 / 2,947.93 / -1.01 / + / +
20 / 4.81 / 4,250 / 1,893.82 / -2.24 / + / ++
21 / 3.77 / 10,680 / 20,403.4 / +1.91 / + / +
22 / 4.04 / 25,000 / 11,035.8 / -2.26 / + / +
aDifference between the predicted (Pred.) and experimental (Exp.) values; ‘+’ indicates that the predicted IC50 value is higher than the experimental IC50 value; ‘-’ indicates that the predicted IC50 value is lower than the experimental IC50 value; a value of 1 indicates that the predicted IC50 value is equal to the experimental IC50 value.
bActivity scale: IC50 < 200 nM = +++ (highly active); 200 nM ≤ IC50 < 2000 nM = ++ (moderately active); IC50 ≥ 2000 nM = + (low active).
Fig. S1 Chemical structures of ACC1 training set compounds and their IC50 values (nM) in parentheses
Table S2 Experimental and predicted IC50 values of ACC2 training set molecules
Compound / FitValue / Exp. IC50 (nM) / Pred. IC50 (nM) / Errora / Exp. scaleb / Pred. scaleb1 / 7.49 / 4 / 3.21 / -1.25 / +++ / +++
2 / 6.91 / 4.5 / 12.10 / +2.69 / +++ / +++
3 / 7.15 / 10 / 6.95 / -1.44 / +++ / +++
4 / 6.94 / 12 / 11.39 / -1.05 / +++ / +++
5 / 6.69 / 20 / 19.90 / -1.01 / +++ / +++
6 / 6.58 / 26 / 26.12 / +1.00 / +++ / +++
7 / 6.35 / 37 / 44.00 / +1.19 / +++ / +++
8 / 5.59 / 47 / 253.02 / +5.38 / +++ / ++
9 / 6.20 / 69 / 62.41 / -1.11 / +++ / +++
10 / 5.09 / 111 / 798.07 / +7.19 / +++ / ++
11 / 5.55 / 227 / 275.75 / +1.21 / ++ / ++
12 / 5.82 / 250 / 150.22 / -1.66 / ++ / +++
13 / 5.64 / 505 / 226.38 / -2.23 / ++ / ++
14 / 5.06 / 530 / 851.20 / +1.61 / ++ / ++
15 / 5.07 / 840 / 834.90 / -1.01 / ++ / ++
16 / 5.05 / 1,200 / 868.22 / -1.38 / ++ / ++
17 / 4.94 / 1,510 / 1142.87 / -1.32 / ++ / ++
18 / 5.08 / 1,620 / 812.52 / -1.99 / ++ / ++
19 / 5.09 / 2,130 / 794.88 / -2.68 / + / ++
20 / 4.61 / 2,420 / 2400.51 / -1.01 / + / +
21 / 4.77 / 3,100 / 1680.65 / -1.84 / + / ++
22 / 3.80 / 26,500 / 15486.10 / -1.71 / + / +
aDifference between the predicted (Pred.) and experimental (Exp.) values; ‘+’ indicates that the predicted IC50 value is higher than the experimental IC50 value; ‘-’ indicates that the predicted IC50 value is lower than the experimental IC50 value; a value of 1 indicates that the predicted IC50 value is equal to the experimental IC50 value.
bActivity scale: IC50 < 200 nM = +++ (highly active); 200 nM ≤ IC50 < 2000 nM = ++ (moderately active); IC50 ≥ 2000 nM = + (low active).
Fig. S2 Chemical structures of ACC2 training set compounds and their IC50 values (nM) in parentheses
Table S3 Experimental and predicted IC50 values of ACC1 inhibitors in the test set
Compound / FitValue / Exp. IC50 (nM) / Pred. IC50 (nM) / Errora / Exp. scaleb / Pred. scaleb1 / 6.30167 / 12 / 61.0705 / -5.09 / +++ / +++
2 / 6.20283 / 16 / 76.6784 / -4.79 / +++ / +++
3 / 6.35244 / 17.5 / 54.332 / -3.10 / +++ / +++
4 / 6.27288 / 18 / 65.2561 / -3.63 / +++ / +++
5 / 6.2056 / 19 / 76.1899 / -4.01 / +++ / +++
6 / 6.34253 / 22 / 55.5868 / -2.53 / +++ / +++
7 / 6.17605 / 23 / 81.5553 / -3.55 / +++ / +++
8 / 6.218 / 26 / 74.0451 / -2.85 / +++ / +++
9 / 6.30947 / 30 / 59.9836 / -2.00 / +++ / +++
10 / 6.17901 / 35 / 81.0013 / -2.31 / +++ / +++
11 / 5.70246 / 36 / 242.681 / -6.74 / +++ / ++
12 / 6.11732 / 42 / 93.3646 / -2.22 / +++ / +++
13 / 6.20882 / 43 / 75.6283 / -1.76 / +++ / +++
14 / 5.84588 / 49 / 174.428 / -3.56 / +++ / +++
15 / 6.27636 / 61 / 64.7351 / -1.06 / +++ / +++
16 / 6.19166 / 65 / 78.6759 / -1.21 / +++ / +++
17 / 6.11735 / 86 / 93.3568 / -1.09 / +++ / +++
18 / 5.77557 / 93 / 205.084 / -2.21 / +++ / ++
19 / 6.0928 / 101 / 98.7879 / +1.02 / +++ / +++
20 / 6.15833 / 102 / 100.942 / +1.01 / +++ / +++
21 / 6.04592 / 104 / 110.047 / -1.06 / +++ / +++
22 / 5.72352 / 110 / 231.196 / -2.10 / +++ / ++
23 / 5.55867 / 120 / 337.93 / -2.82 / +++ / ++
24 / 5.79556 / 140 / 191.918 / -1.37 / +++ / +++
25 / 6.06352 / 172 / 105.678 / +1.63 / +++ / +++
26 / 5.60498 / 210 / 303.752 / -1.45 / ++ / ++
27 / 5.72949 / 220 / 212.942 / +1.03 / ++ / ++
28 / 5.53976 / 230 / 351.138 / -1.53 / ++ / ++
29 / 5.35075 / 303 / 545.44 / -1.80 / ++ / ++
30 / 5.57804 / 319 / 323.195 / -1.01 / ++ / ++
31 / 6.18849 / 366 / 79.2518 / +4.62 / ++ / +++
32 / 5.38593 / 370 / 597.717 / -1.62 / ++ / ++
33 / 5.49007 / 390 / 395.761 / -1.01 / ++ / ++
34 / 5.27467 / 451 / 396.986 / +1.14 / ++ / ++
35 / 4.27269 / 562 / 6,528.47 / -11.62 / ++ / +
36 / 4.27416 / 590 / 6,940 / -11.76 / ++ / +
37 / 4.19517 / 620 / 7,804.27 / -12.59 / ++ / +
38 / 4.26985 / 634 / 6,571.32 / -10.36 / ++ / +
39 / 4.26187 / 650 / 6,693.14 / -10.30 / ++ / +
40 / 5.38726 / 663 / 501.467 / +1.32 / ++ / ++
41 / 5.26986 / 670 / 664.723 / +1.01 / ++ / ++
42 / 4.20942 / 700 / 7,552.23 / -10.79 / ++ / +
43 / 5.20845 / 760 / 756.914 / +1.00 / ++ / ++
44 / 4.38503 / 766 / 121.4 / +6.31 / ++ / +++
45 / 4.27416 / 800 / 7,804.27 / -9.76 / ++ / +
46 / 4.27416 / 850 / 6,506.43 / -7.65 / ++ / +
47 / 4.24614 / 910 / 6,940 / -7.63 / ++ / +
48 / 4.97308 / 920 / 1,301.42 / -1.41 / ++ / ++
49 / 5.02083 / 940 / 1,223.66 / -1.30 / ++ / ++
50 / 3.75342 / 1,100 / 21,581.3 / -19.62 / ++ / +
51 / 5.04541 / 1,120 / 823.167 / +1.36 / ++ / ++
52 / 5.17048 / 1,140 / 826.083 / +1.38 / ++ / ++
53 / 5.05409 / 1,150 / 1,079.96 / +1.06 / ++ / ++
54 / 4.27416 / 1,200 / 1,737.65 / -1.45 / ++ / ++
55 / 5.17137 / 1,250 / 871.147 / +1.43 / ++ / ++
56 / 4.5673 / 1,280 / 3,466.18 / -2.71 / ++ / +
57 / 4.24122 / 1,320 / 7,019.11 / -5.32 / ++ / +
58 / 4.66364 / 1,350 / 2,653.73 / -1.97 / ++ / +
59 / 4.27174 / 1,390 / 6,542.72 / -4.71 / ++ / +
60 / 4.27754 / 1,620 / 6,455.92 / -3.99 / ++ / +
61 / 4.63645 / 1,800 / 2,825.22 / -1.57 / ++ / +
62 / 4.26324 / 1,830 / 6,672.07 / -3.65 / ++ / +
63 / 4.2912 / 2,060 / 6,256.05 / -3.04 / + / +
64 / 4.25817 / 2,100 / 1,301.42 / +1.61 / + / ++
65 / 4.77924 / 2,120 / 2,274.08 / -1.07 / + / +
66 / 4.29211 / 2,210 / 6,242.91 / -2.82 / + / +
67 / 4.69563 / 2,300 / 2,465.32 / -1.07 / + / +
68 / 3.97248 / 2,490 / 13,032.2 / -5.23 / + / +
69 / 4.66286 / 2,900 / 2,658.51 / +1.09 / + / +
70 / 4.46385 / 2,970 / 4,203.86 / -1.42 / + / +
71 / 4.69563 / 3,000 / 3,291.72 / -1.10 / + / +
72 / 4.67681 / 3,110 / 2,574.47 / +1.21 / + / +
73 / 4.25817 / 3,200 / 7,804.27 / -2.44 / + / +
74 / 4.22471 / 3,700 / 7,291.11 / -1.97 / + / +
75 / 4.27312 / 3,780 / 6,521.94 / -1.73 / + / +
76 / 4.19049 / 3,900 / 7,888.85 / -2.02 / + / +
77 / 4.33491 / 4,200 / 5,657.08 / -1.35 / + / +
78 / 4.25817 / 4,250 / 6,750.41 / -1.59 / + / +
79 / 4.29898 / 5,700 / 6,144.93 / -1.08 / + / +
80 / 4.26047 / 6,790 / 6,810.22 / +1.00 / + / +
81 / 4.57008 / 7,400 / 7,149.14 / +1.04 / + / +
82 / 4.08849 / 8,150 / 9,977.29 / -1.22 / + / +
83 / 4.24498 / 8,580 / 6,958.57 / +1.23 / + / +
84 / 4.09459 / 9,900 / 9,837.97 / +1.01 / + / +
85 / 4.25817 / 10,500 / 10,516.4 / +1.00 / + / +
86 / 4.69563 / 11,000 / 11,075.9 / -1.01 / + / +
87 / 3.67005 / 12,700 / 12,113.6 / +1.05 / + / +
88 / 3.94028 / 14,000 / 14,205 / -1.01 / + / +
89 / 3.74367 / 21,000 / 20,131.8 / +1.04 / + / +
aDifference between the predicted (Pred.) and experimental (Exp.) values; ‘+’ indicates that the predicted IC50 value is higher than the experimental IC50 value; ‘-’ indicates that the predicted IC50 value is lower than the experimental IC50 value; a value of 1 indicates that the predicted IC50 value is equal to the experimental IC50 value.
bActivity scale: IC50 < 200 nM = +++ (highly active); 200 nM ≤ IC50 < 2000 nM = ++ (moderately active); IC50 ≥ 2000 nM = + (low active).
Fig. S3 Chemical structures and IC50 value of ACC1 test set compounds
Table S4 Experimental and predicted IC50 values of ACC2 inhibitors in the test set
Compound / FitValue / Exp. IC50 (nM) / Pred. IC50 (nM) / Errora / Exp. scaleb / Pred. scaleb1 / 7.01748 / 9 / 9.45 / -1.05 / +++ / +++
2 / 6.67816 / 15 / 20.65 / -1.38 / +++ / +++
3 / 6.7487 / 16 / 17.56 / -1.10 / +++ / +++
4 / 5.25301 / 28 / 549.65 / -19.63 / +++ / ++
5 / 6.39859 / 34 / 39.31 / -1.16 / +++ / +++
6 / 6.6781 / 35 / 20.65 / +1.69 / +++ / +++
7 / 6.62073 / 38 / 23.57 / +1.61 / +++ / +++
8 / 6.16748 / 55 / 66.93 / -1.22 / +++ / +++
9 / 6.22774 / 57 / 58.26 / -1.02 / +++ / +++
10 / 6.30942 / 60 / 50.92 / +1.18 / +++ / +++
11 / 6.24859 / 67 / 55.53 / +1.21 / +++ / +++
12 / 6.74426 / 70 / 17.74 / +3.95 / +++ / +++
13 / 5.45623 / 71 / 344.25 / -4.85 / +++ / ++
14 / 5.96517 / 81 / 106.64 / -1.32 / +++ / +++
15 / 5.62139 / 96 / 235.35 / -2.45 / +++ / ++
16 / 5.96825 / 98 / 70.87 / +1.38 / +++ / +++
17 / 4.74154 / 100 / 879.96 / -8.80 / +++ / ++
18 / 4.94522 / 102 / 1116.56 / -10.95 / +++ / ++
19 / 5.10972 / 113 / 764.51 / -6.77 / +++ / ++
20 / 5.0402 / 117 / 897.22 / -7.67 / +++ / ++
21 / 5.0918 / 126 / 796.71 / -6.32 / +++ / ++
22 / 6.156 / 130 / 68.72 / +1.89 / +++ / +++
23 / 6.2278 / 140 / 58.25 / +2.40 / +++ / +++
24 / 5.36523 / 141 / 424.49 / -3.01 / +++ / ++
25 / 5.84431 / 150 / 140.86 / +1.06 / +++ / +++
26 / 5.80546 / 151 / 141.58 / +1.07 / +++ / +++
27 / 6.02182 / 156 / 93.60 / +1.67 / +++ / +++
28 / 5.73376 / 164 / 181.69 / -1.11 / +++ / +++
29 / 5.96403 / 190 / 106.92 / +1.78 / +++ / +++
30 / 5.04591 / 200 / 885.51 / -4.43 / ++ / ++
31 / 5.79689 / 202 / 157.11 / +1.29 / ++ / +++
32 / 5.04429 / 210 / 888.82 / -4.23 / ++ / ++
33 / 5.25257 / 214 / 119.27 / +1.79 / ++ / +++
34 / 5.38748 / 220 / 403.29 / -1.83 / ++ / ++
35 / 5.43775 / 260 / 359.21 / -1.38 / ++ / ++
36 / 4.95392 / 268 / 1094.40 / -4.08 / ++ / ++
37 / 5.0701 / 270 / 837.54 / -3.10 / ++ / ++
38 / 5.01448 / 274 / 951.97 / -3.47 / ++ / ++
39 / 4.72837 / 290 / 1839.61 / -6.34 / ++ / ++
40 / 5.07115 / 303 / 835.52 / -2.76 / ++ / ++
41 / 5.43445 / 330 / 361.95 / -1.10 / ++ / ++