SUPPLEMENTARY DATA Structure-based virtual

SUPPLEMENTARY DATA

Structure-based virtual screening and molecular dynamics simulations offer novel natural compounds as potential inhibitors of Mycobacterium tuberculosis isocitrate lyase

Rohit Shukla#, Harish Shukla#, Amit Sonkar, Tripti Pandey, and Timir Tripathi*

Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong 793022, India

1

Supplementary Figure 1. Interaction between MtbICL and the reference compounds.

2

Supplementary Table 1: Table represents the Lipinski rule of five. Parameters were taken from ZINC database. Selected 27compounds with reference ligands are highlighted in bold.

Sr. No. 1. 2.

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

ZINC ID

Molecular weight (g/mol) Bromopyruvate 165.95 Nitropropionat 118.068 e ZINC30725806 586.689 ZINC56871207 586.689 ZINC30725812 586.689 ZINC30724164 503.126 ZINC08215755 503.15 ZINC16052058 537.233 ZINC95618132 802.688 ZINC15280332 537.233 ZINC12402869 519.149 ZINC32789745 586.689 ZINC28957444 522.578 ZINC18007499 582.657 ZINC95100378 730.835 ZINC53276076 580.641 ZINC08295117 501.178 ZINC08215530 504.134 ZINC13473520 502.186 ZINC08215662 487.151 ZINC68572914 605.551 ZINC60094177 520.157 ZINC18456332 503.15 ZINC03983911 580.641

XlogP

H-bond acceptor

Rotatable Bonds

-0.53 -0.39

Hbond donor 0 0

3 5

2 3

4.50 4.50 4.50 -4.37 -4.55 -2.91 -3.16 -2.91 -4.53 4.50 2.12 5.30 8.73 4.82 -3.48 -4.41 -3.48 -3.58 5.63 -4.22 -3.54 4.82

3 3 3 2 4 7 12 7 5 3 4 4 2 3 4 3 5 3 3 6 4 3

10 10 10 18 18 18 22 18 19 10 10 10 8 10 17 18 17 17 16 19 18 10

13 13 13 8 8 8 12 8 8 13 10 12 8 11 8 8 8 8 11 8 8 11

3

25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55.

ZINC30320675 ZINC15878789 ZINC08444972 ZINC06879053 ZINC08217391 ZINC70712237 ZINC13508937 ZINC68568879 ZINC77301904 ZINC12496167 ZINC08215481 ZINC24424495 ZINC04293328 ZINC03871961 ZINC70681081 ZINC02138703 ZINC95612014 ZINC08398287 ZINC02135897 ZINC68568482 ZINC02130997 ZINC02129751 ZINC30320734 ZINC13508104 ZINC70712214 ZINC70712316 ZINC09435164 ZINC84758235 ZINC12405084 ZINC70704586 ZINC02128675

603.327 537.233 604.671 531.477 537.233 618.709 471.152 577.505 598.036 488.135 440.178 521.234 629.116 593.648 562.574 495.895 548.606 642.621 497.911 566.512 531.928 475.577 587.328 499.456 618.709 578.644 520.547 546.937 425.163 585.06 483.884

-5.01 -2.91 6.43 6.04 -2.91 3.09 -2.66 8.36 2.49 -4.43 -3.69 -1.75 7.86 0.32 6.98 1.33 8.12 4.80 2.22 -0.13 2.71 1.10 -4.55 -2.84 3.11 2.07 6.67 2.20 -3.49 3.90 1.83

9 7 2 0 7 1 2 0 4 2 5 6 0 3 0 3 0 2 3 4 3 3 8 6 1 1 2 5 3 3 3

21 18 12 12 18 13 16 12 13 17 16 17 8 16 8 9 8 1 9 14 9 9 20 13 13 13 8 9 15 9 9

9 8 13 12 8 14 8 9 10 8 6 8 10 12 9 7 7 14 9 11 8 7 8 11 14 14 9 9 6 7 8

4

56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86.


665.171 424.179 560.558 576.601 587.328 535.75 489.504 530.544 489.504 548.563 536.445 562.574 596.541 388.372 756.663 487.488 419.441 569.017 455.213 516.565 541.597 408.18 716.604 730.835 548.547 533.462 456.451 482.525 484.504 434.397 576.427

7.25 -3.73 7.49 7.50 -4.55 7.44 1.47 5.47 1.47 6.98 0.93 6.49 -0.01 3.00 -1.76 2.00 2.17 4.69 -5.43 6.23 6.02 -2.57 1.62 8.82 6.59 0.62 2.20 -1.04 4.81 -0.30 4.62

0 4 0 0 8 1 3 2 3 3 5 0 5 0 12 3 3 3 5 4 1 3 7 2 0 5 2 8 0 5 0

9 15 8 8 20 5 9 10 9 12 12 8 13 8 20 9 9 9 16 10 10 14 16 8 8 13 10 13 7 10 18

10 6 9 9 8 8 7 6 7 10 9 9 11 10 8 7 8 6 6 9 10 6 14 8 8 9 10 9 7 7 10

5

87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117.


590.057 634.508 478.477 810.783 453.383 605.672 447.5 527.533 553.522 555.587 544.603 599.596 461.45 560.558 557.515 574.517 472.462 546.531 394.391 596.68 463.125 585.06 486.524 422.44 599.596 569.977 471.445 556.531 469.493 443.455 555.612

6.25 6.38 1.61 9.13 0.27 6.76 2.73 2.94 3.00 3.84 8.30 5.37 0.73 7.01 4.02 4.65 0.61 7.12 1.00 5.16 -4.50 3.92 4.50 7.82 5.37 3.51 1.36 4.18 5.80 5.00 5.57

0 0 3 2 3 0 1 4 3 4 0 1 3 0 1 1 8 0 3 2 3 3 2 0 1 3 2 2 0 0 0

9 9 9 16 11 9 9 10 9 10 6 12 9 8 12 11 14 8 10 9 16 9 8 6 12 9 9 12 7 7 9

9 9 7 12 8 9 6 6 7 7 8 11 7 9 11 11 8 8 7 13 8 7 9 8 11 7 8 11 7 6 9

6

118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148.


711.366 571.542 496.743 334.28 518.493 501.515 530.964 484.504 385.427 558.677 477.493 541.536 507.58 562.574 500.503 464.109 441.255 442.263 430.456 587.328 516.51 500.511 483.884 476.481 449.439 592.048 507.58 547.55 575.999 548.599 532.548

-0.61 4.25 9.03 1.38 4.15 2.38 7.29 4.81 3.30 1.43 1.99 2.52 5.87 7.36 5.27 -4.59 -1.91 -0.74 5.56 -4.45 2.63 2.97 1.83 4.36 1.13 3.18 5.87 6.75 4.65 4.49 7.35

3 1 2 0 0 3 2 0 3 3 3 3 1 0 0 2 4 6 0 8 0 0 3 0 3 4 1 2 5 3 0

20 12 4 8 8 9 8 7 7 10 9 10 10 8 8 16 14 14 6 20 11 10 9 8 9 10 10 12 9 9 7

13 11 10 6 8 7 9 7 6 11 9 9 10 9 8 8 6 6 9 9 8 7 8 10 7 7 10 10 11 6 8

7

149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174. 175. 176. 177. 178. 179.


567.549 475.477 560.558 509.922 476.481 729.692 505.547 522.566 498.487 470.477 536.445 469.426 569.977 489.504 488.54 506.551 571.63 419.414 564.537 355.262 576.427 471.513 503.531 449.439 556.531 528.634 543.62 415.401 421.541 424.179 479.124

3.37 1.10 7.14 1.70 4.10 4.62 2.91 0.31 5.79 4.45 1.57 0.02 3.51 1.47 3.97 4.70 3.04 2.20 -3.42 0.97 4.62 2.89 2.23 1.13 4.18 5.08 3.83 4.25 4.05 -2.53 -4.48

3 3 0 3 0 0 3 3 0 0 5 3 3 3 2 3 4 3 9 0 0 2 3 3 2 2 2 0 2 4 4

9 9 8 9 8 14 9 12 8 7 12 11 9 9 8 8 10 9 15 10 18 8 9 9 12 8 9 7 6 15 17

7 7 7 7 9 14 10 9 8 7 9 10 7 7 9 10 8 8 9 4 10 6 7 7 11 8 11 5 9 6 8

8

180. 181. 182. 183. 184. 185. 186. 187. 188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 208. 209. 210.


535.532 448.364 489.504 576.526 401.426 587.328 578.021 750.809 486.476 470.877 441.448 402.399 542.613 526.506 452.439 527.529 485.492 610.07 486.426 419.441 502.548 275.199 522.605 372.373 478.497 541.536 509.448 489.504 449.439 421.382 477.493

2.83 2.29 1.47 3.46 3.38 -3.45 2.81 9.25 4.61 4.59 1.46 2.91 4.76 0.86 1.69 6.34 4.98 5.44 -2.10 2.05 4.42 3.26 4.34 3.94 4.44 2.15 6.78 1.87 1.22 0.43 1.98

3 0 3 1 3 8 4 2 0 3 6 0 2 5 1 1 0 0 6 3 2 2 3 0 0 2 1 3 3 2 3

9 9 9 12 8 20 10 8 8 12 12 8 8 14 9 9 8 10 13 9 8 2 8 7 8 10 10 9 9 11 9

7 6 7 14 6 9 7 12 8 7 8 10 8 9 8 9 7 8 7 8 8 3 9 8 10 10 10 7 8 11 8

9

211. 212. 213. 214. 215. 216. 217. 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238. 239. 240. 241.


595.53 467.586 463.466 438.52 461.45 470.479 475.477 509.922 483.52 405.386 483.52 474.557 445.451 459.463 459.463 477.493 484.366 414.461 464.626 440.452 465.166 570.349 434.497 469.857 592.981 405.367 553.522 450.525 464.478 522.608 500.503

-3.49 3.72 1.51 6.50 0.73 0.84 1.09 1.70 6.11 0.88 4.66 4.14 1.23 0.78 0.78 1.96 -0.31 5.92 4.16 2.95 -3.77 1.31 2.05 1.36 3.97 -0.61 3.00 3.23 1.59 5.53 5.67

10 2 3 0 3 1 3 3 0 2 0 2 2 6 6 3 9 2 2 2 2 0 2 3 1 5 3 1 2 2 0

15 7 9 6 9 9 9 9 7 8 7 7 8 13 13 9 14 6 5 9 15 13 7 9 12 12 9 8 10 8 8

6 10 7 10 7 9 7 7 7 7 8 10 7 8 8 8 7 8 7 9 8 11 8 7 14 8 7 6 9 8 8

10

242. 243. 244. 245. 246. 247. 248. 249. 250. 251. 252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268. 269. 270. 271. 272.


469.493 455.466 468.367 631.793 523.467 530.576 446.455 405.414 545.567 522.569 487.691 458.514 532.548 467.41 532.548 464.498 483.52 497.911 469.426 548.547 361.183 477.354 584.676 564.642 596.043 475.24 516.625 541.536 532.548 530.636 411.41

5.74 5.42 0.35 -2.46 -0.38 8.38 4.51 2.15 2.78 -4.94 3.26 4.38 6.85 -0.69 6.85 3.08 6.17 2.19 0.42 6.99 -2.39 0.77 4.59 4.30 5.00 -4.47 4.25 1.75 7.33 7.26 3.74

0 0 8 0 5 0 0 4 3 6 2 2 0 3 0 2 0 3 3 0 3 7 3 3 0 6 2 2 0 4 0

7 7 13 10 13 6 7 9 9 14 6 7 7 11 7 9 7 9 11 8 13 13 8 9 10 16 7 10 7 9 8

7 6 7 12 9 7 8 8 7 9 12 8 8 9 8 9 7 8 10 8 4 7 8 7 8 10 5 10 8 8 8

11

273. 274. 275. 276. 277. 278. 279. 280. 281. 282. 283. 284. 285. 286. 287. 288. 289. 290. 291. 292. 293. 294. 295. 296. 297. 298. 299. 300. 301. 302. 303.


453.494 544.65 721.675 598.429 510.481 421.385 391.403 596.494 551.02 463.466 512.591 469.857 516.575 444.439 434.444 493.444 587.328 508.538 394.379 430.381 483.884 483.84 578.573 520.65 522.566 596.704 521.526 623.504 469.585 637.432 431.409

5.77 0.90 5.86 4.14 0.06 0.38 -0.63 -1.64 5.40 1.51 3.65 1.36 4.79 4.64 5.18 3.01 -4.45 8.99 4.11 0.72 1.73 1.74 6.58 4.68 0.31 5.05 2.00 4.42 4.25 4.10 0.10

0 3 1 2 3 3 0 10 2 3 3 3 2 0 0 6 8 2 0 6 3 3 0 4 3 2 2 1 2 1 7

6 10 15 8 14 9 7 16 8 9 8 9 8 7 7 10 20 10 7 14 9 9 9 8 12 9 11 10 6 12 13

6 10 15 7 12 7 8 6 8 7 7 7 8 8 9 9 9 11 8 6 7 7 9 9 9 12 9 8 8 14 6

12

304. 305. 306. 307. 308. 309. 310. 311. 312. 313. 314. 315. 316. 317. 318. 319. 320. 321. 322. 323. 324. 325. 326. 327. 328. 329. 330. 331. 332. 333. 334.


555.519 477.493 580.502 505.547 558.677 514.45 475.521 480.108 499.452 603.327 518.521 426.425 441.448 340.384 548.556 358.346 536.649 392.415 370.405 520.498 430.412 444.56 494.477 467.59 522.557 558.536 476.481 476.481 506.559 419.441 459.478

1.63 1.99 5.69 2.91 1.40 4.53 2.86 -4.57 0.01 -5.01 6.98 2.59 1.46 -4.61 3.25 3.58 4.02 2.84 3.86 0.18 4.92 4.79 6.90 1.10 6.65 3.29 5.47 6.39 2.41 1.75 1.61

3 3 0 3 3 2 2 3 3 9 0 2 6 8 4 0 5 2 1 4 0 2 1 5 2 1 0 0 4 4 2

11 9 14 9 10 12 8 17 12 21 7 9 12 10 13 7 9 8 7 12 7 6 8 8 8 12 8 8 10 9 8

8 9 16 10 11 8 9 8 11 9 7 9 8 11 8 8 9 7 8 7 6 6 10 9 9 14 11 10 8 9 7

13

335. 336. 337. 338. 339. 340. 341. 342.

ZINC04027376 ZINC08964851 ZINC01799169 ZINC02130322 ZINC85879954 ZINC08917927 ZINC08790313 ZINC04235228

414.41 430.381 398.411 535.532 430.381 461.474 483.453 505.647

3.53 0.69 3.28 2.83 0.72 2.18 -0.54 7.55

0 6 0 3 6 2 3 1

8 14 7 9 14 9 11 6

10 6 10 7 6 7 11 8

14

Supplementary Table 2- The tabulated absorption and distribution properties obtained from admetSAR server for all the 340 compounds. Selected 27compounds with reference ligands are highlighted in bold. Sr. No.

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.

ZINC ID

BBB probability

Bromopyruvat e Nitropropionat e ZINC30725806 ZINC56871207 ZINC30725812 ZINC30724164 ZINC08215755 ZINC16052058 ZINC95618132 ZINC15280332 ZINC12402869 ZINC32789745 ZINC28957444 ZINC18007499 ZINC95100378 ZINC53276076 ZINC08295117 ZINC08215530 ZINC13473520 ZINC08215662 ZINC68572914

+/0.9694

HIACaco-2 probability permeabili ty probabilit y +/0.9234 -/0.5470

Caco-2 permeabilit y

P-gp substrate

P-gp inhibitor

0.6985

Non-substrate/0.8857

Non-inhibitor/0.9512

+/0.8470

+/0.7946

-/0.5500

0.5026

Non-substrate/0.8506

Non-inhibitor/0.9893

-/0.5806 -/0.5806 -/0.5806 +/0.7460 +/0.8501 +/0.8568 -/0.9026 +/0.8568 +/0.9158 -/0.5806 -/0.6719 +/0.5313 +/0.7254 +/0.7005 +/0.9183 +/0.7985 +/0.8828 +/0.9289 -/0.6468

-/0.7723 -/0.7723 -/0.7723 +/0.7072 +/0.6930 -/0.8250 +/0.7849 -/0.8250 -/0.8012 -/0.7723 +/0.9940 -/0.7984 +/0.9872 -/0.9403 -/0.9182 -/0.8009 -/0.9639 +/0.5081 -/0.5245

-/0.8206 -/0.8206 -/0.8206 -/0.7572 -/0.7227 -/0.6925 -/0.8296 -/0.6925 -/0.7519 -0.8206 -/0.5989 -/0.8472 -/0.5522 -/0.8249 -/0.7264 -/0.7831 -/0.7136 -/0.6978 -/0.5466

0.1471 0.1471 0.1471 -0.1707 -0.3731 -0.4913 -0.6612 -0.4913 -0.5575 0.1471 0.6416 0.2510 1.0289 0.3850 -0.2396 -0.4850 -0.5333 -0.2263 0.7814

Substrate/0.6955 Substrate/0.6955 Substrate/0.6955 Non-substrate/0.5781 Non-substrate/0.5260 Non-substrate/0.7118 Substrate/0.7829 Non-substrate/0.7118 Non-substrate/0.5980 Substrate/0.6955 Substrate/0.7626 Substrate/0.6260 Non-substrate/0.6068 Substrate/0.5089 Non-substrate/0.5937 Non-substrate/0.6439 Non-substrate/0.6443 Non-substrate/0.6368 Non-substrate/0.6432

Non-inhibitor/0.7412 Non-inhibitor/0.7412 Non-inhibitor/0.7412 Non-inhibitor/0.8473 Non-inhibitor/0.9473 Non-inhibitor/0.9946 Non-inhibitor/0.8747 Non-inhibitor/0.9946 Non-inhibitor/0.9746 Non-inhibitor/0.8790 Non-inhibitor/0.9617 Non-inhibitor/0.9073 Non-inhibitor/0.5652 Non-inhibitor/0.8361 Non-inhibitor/0.9596 Non-inhibitor/0.8905 Non-inhibitor/0.9715 Non-inhibitor/0.9292 Non-inhibitor/0.9240

15

22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52.


+/0.8852 +/0.9179 +/0.7005 +/0.7631 +/0.8568 +/0.5604 +/0.9653 +/0.8568 +/0.5700 +/0.9880 +/0.9525 -/0.9706 +/0.6784 +/0.9158 +/0.8749 +/0.8860 -/0.9621 +/0.6679 -/0.5789 +/0.9844 +/0.9677 -/0.8324 -/0.6257 -/0.5136 -/0.6721 +/0.5661 -/0.8242 +/0.5700 +/0.6056 +/0.7839 +/0.8326

-/0.9492 -/0.8701 -/0.9403 -/0.9544 -/0.8250 +/0.7968 +/0.9528 -/0.8250 +/0.9674 +/0.6457 +/0.9747 +/0.7308 +/0.6946 -/0.8012 -/0.9371 +/1.0000 +/0.7462 +/1.0000 -/0.6563 +/1.0000 +1.0000 +/0.7842 +/0.6462 +/0.7141 -/0.6124 -/0.9284 -/0.9873 +/0.9674 +/0.9522 +/0.8516 +/1.0000

-/0.7277 -/0.7487 -/0.8249 -/0.7458 -/0.6925 +/0.5486 -/0.5140 -/0.6925 -/0.5570 -/0.6254 +/0.5443 -0.6505 -/0.7577 -/0.7519 -0.6859 +/0.5292 -/0.6816 +/0.7247 -/0.7280 +/0.5128 -/0.6197 -/0.6798 -/0.8468 -/0.7244 -/0.7743 -/0.7419 -/0.6871 -/0.5570 -/0.5827 +/0.6195 -/0.6352

-0.6014 -0.4812 0.3850 -0.8833 -0.4913 1.1703 1.2989 -0.4913 0.8315 0.0060 1.1775 0.2091 -0.3027 -0.5575 -0.6079 1.1838 0.1536 1.1454 0.1625 1.5246 1.1151 0.4042 -0.6074 0.0083 0.1678 -0.6635 -0.4107 0.8315 0.8743 1.2718 0.6234

Non-substrate/0.6847 Non-substrate/0.6832 Substrate/0.5089 Non-substrate/0.5275 Non-substrate/0.7118 Non-substrate/0.5899 Non-substrate/0.7506 Non-substrate/0.7118 Non-substrate/0.6116 Non-substrate/0.7565 Non-substrate/0.8340 Non-substrate/0.7247 Non-substrate/0.5717 Non-substrate/0.5980 Non-substrate/0.7559 Non-substrate/0.8202 Substrate/0.8279 Substrate/0.5317 Substrate/0.5725 Non-substrate/0.6556 Non-substrate/0.5346 Substrate/0.6459 Substrate/0.8330 Non-substrate/0.5369 Substrate/0.6707 Substrate/0.5280 Substrate/0.7017 Non-substrate/0.6116 Substrate/0.5263 Non-substrate/0.6920 Non-substrate/0.6802

Non-inhibitor/0.9833 Non-inhibitor/0.9537 Non-inhibitor/0.8361 Non-inhibitor/0.9777 Non-inhibitor/0.9946 Non-inhibitor/0.8625 Non-inhibitor/0.9483 Non-inhibitor/0.9946 Non-inhibitor/0.6687 Non-inhibitor/0.7671 Non-inhibitor/0.6577 Non-inhibitor/0.8689 Non-inhibitor/0.7607 Non-inhibitor/0.9746 Non-inhibitor/0.9933 Inhibitor/0.6140 Inhibitor/0.6082 Inhibitor/0.8995 Non-inhibitor/0.7666 Inhibitor/0.8268 Non-inhibitor/0.7962 Non-inhibitor/0.8905 Non-inhibitor/0.9666 Non-inhibitor/0.7479 Non-inhibitor/0.8530 Non-inhibitor/0.9790 Inhibitor/0.6388 Inhibitor/0.6687 Non-inhibitor/0.6727 Non-inhibitor/0.8030 Non-inhibitor/0.8125

16

53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83.


+/0.7985 -/0.8011 -/0.7893 +/0.7085 +/0.5801 +/0.6975 +/0.7163 +/0.5661 +/0.7826 -/0.5139 +/0.5361 -/0.7339 +/0.6420 +/0.7558 +/0.8510 +/0.7791 +/0.9188 -/0.8791 -/0.7023 +/0.7091 -/0.7633 +/0.7406 +/0.6560 +/0.5338 +/0.9289 +/0.7558 +/0.7529 +/0.6679 -/0.8690 -/0.8147 +/0.6793

-/0.8009 +/0.9201 +/0.7664 +/0.9949 +/0.6930 +/1.0000 +/0.9956 -/0.9284 +/0.8799 -/0.6996 +/0.5600 -/0.6607 -/0.5749 +/0.6037 +/0.9894 +/0.6179 +/0.9841 +/0.7583 -/0.6166 +/0.9973 +/0.9766 -/0.8106 +/0.8564 +/1.0000 +/5081 +/0.6037 +/0.9849 +/1.0000 -/0.9698 +/0.9902 -/0.8434

-/0.7831 -/0.6535 -/0.6805 -/0.5175 -/0.7227 +/0.6872 +/0.6938 -/0.7419 -/0.6064 -/0.7877 -/5569 -/0.7818 -/5175 -/0.8294 +/0.7623 -/0.6871 +/0.6500 -/0.9124 -/0.7490 -/0.6716 -/0.6500 -/0.7298 +/5568 -/0.6253 -/0.6978 -/0.8294 -/0.5772 +/0.7247 -/0.8139 -/0.6279 -/0.6640

-0.4850 0.4499 0.2644 0.4423 -0.3731 1.0131 1.0846 -0.6635 1.1127 -0.0081 0.3982 0.0609 0.9502 -0.7657 1.1549 -0.1788 1.2280 -0.5327 0.0949 0.5424 0.3597 -0.4446 -2.9010 0.5896 -0.2263 -0.7657 0.9390 1.1454 -0.4631 0.5706 -0.4159

Non-substrate/0.6439 Substrate/0.8158 Substrate/0.6067 Non-substrate/0.8710 Non-substrate/0.5260 Substrate/0.5392 Non-substrate/0.5141 Substrate/0.5280 Substrate/0.6507 Substrate/0.7029 Substrate/0.5203 Substrate/0.6913 Non-substrate/0.5387 Substrate/0.5687 Substrate/0.5075 Substrate/0.5849 Substrate/0.6187 Substrate/0.6909 Substrate/0.6195 Substrate/0.6693 Substrate/0.6648 Non-substrate/0.5093 Non-substrate/0.7217 Substrate/0.5569 Non-substrate/0.6368 Substrate/0.5687 Non-substrate/0.6368 Substrate/0.5317 Substrate/0.7136 Substrate/0.5458 Substrate/0.5724

Non-inhibitor/0.8905 Non-inhibitor/0.5438 Non-inhibitor/0.9559 Non-inhibitor/0.5883 Non-inhibitor/0.9473 Inhibitor/0.8730 Inhibitor/0.9300 Non-inhibitor/0.9790 Non-inhibitor/0.5082 Non-inhibitor/0.7164 Non-inhibitor/0.9764 Non-inhibitor/0.6550 Non-inhibitor/0.8431 Inhibitor/0.5426 Inhibitor/0.8604 Non-inhibitor/0.5696 Inhibitor/0.5738 Non-inhibitor/0.8495 Non-inhibitor/0.8115 Non-inhibitor/0.5000 Non-inhibitor/0.9087 Non-inhibitor/0.9845 Non-inhibitor/0.8673 Inhibitor/0.9416 Non-inhibitor/0.9292 Inhibitor/0.5426 Non-inhibitor/0.9292 Inhibitor/0.8995 Non-inhibitor/0.7504 Non-inhibitor/0.8995 Non-inhibitor/0.5159

17

84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114.


+/0.7441 +/0.6452 +/0.8265 +/0.6712 +/0.7130 -/0.8218 +/0.7394 -/0.6761 +/0.7737 +/0.6627 -/0.9179 +/0.5196 -/0.9418 +/0.8997 +/0.8532 +/0.5342 +/0.8642 +/0.9459 +/0.9652 +/0.5861 +/0.7809 +/0.9461 -/0.9489 +/0.9467 -/0.8011 +/0.7451 +/0.9150 +/0.8532 -/0.5447 +/0.7426 +/0.9836

+/0.9904 -/0.7445 -/0.6831 +/0.9961 +/0.9942 -/0.8357 +/0.8828 +/0.5698 +/1.0000 +/0.9893 +/0.8298 +/0.8801 +/7845 +/0.9957 +/0.9936 -/0.7342 +/0.9903 +/0.9925 +/0.9768 +/0.9921 +/1.0000 +/0.9953 +/0.9579 -/0.5674 +/0.9201 +/0.8936 +/0.9740 +/0.9936 +/0.8809 +/0.8885 +/0.9970

+/0.7038 -/0.8258 -/0.5560 -/0.5261 -/0.5335 -/0.7823 -/0.5284 -/0.6455 -/0.5554 -/0.5611 -/0.6588 -/0.6851 -/0.6756 +/6318 -/0.6782 -/7863 +/0.7266 -/0.7085 -/0.7391 -/0.7061 +/0.6979 -/0.6756 -/0.7259 -/0.7415 -/0.6535 -/0.6951 +/0.5000 -/0.6782 -/0.6788 -/0.6838 -/0.6715

1.2301 -0.6175 0.7247 1.1636 1.1390 -0.1948 0.8838 0.1397 1.1672 1.1941 0.2434 0.0263 0.1959 1.0233 1.0183 0.0357 1.0187 0.8592 0.7806 0.0250 0.9647 0.2673 1.1619 0.0508 0.4499 0.5627 0.7605 1.0183 0.0697 0.2038 0.8034

Substrate/0.6060 Substrate/0.6640 Non-substrate/0.6157 Non-substrate/0.8715 Non-substrate/0.8672 Substrate/0.6654 Non-substrate/0.5552 Non-substrate/0.5320 Non-substrate/0.8391 Non-substrate/0.7499 Substrate/0.7620 Substrate/0.5890 Substrate/0.7634 Substrate/0.5402 Non-substrate/0.7709 Substrate/0.5937 Substrate/0.5150 Non-substrate/0.8224 Non-substrate/0.8500 Substrate/0.6286 Non-substrate/0.5122 Substrate/0.5495 Substrate/0.7101 Non-substrate/0.7327 Substrate/0.8158 Substrate/0.6513 Non-substrate/0.8249 Non-substrate/0.7709 Substrate/0.6513 Substrate/0.5112 Non-substrate/0.8247

Inhibitor/0.8618 Non-inhibitor/0.8218 Non-inhibitor/0.7681 Inhibitor/0.5928 Inhibitor/0.6860 Non-inhibitor/0.7425 Non-Inhibitor/0.6260 Non-Inhibitor/0.7591 Inhibitor/0.8541 Inhibitor/0.8804 Non-Inhibitor/0.8526 Non-Inhibitor/0.9667 Non-Inhibitor/0.8252 Inhibitor/0.8360 Non-Inhibitor/0.6308 Non-inhibitor/0.7749 Inhibitor/0.7859 Non-Inhibitor/0.7098 Inhibitor/0.6262 Non-inhibitor/0.9379 Inhibitor/0.8017 Non-inhibitor/0.8223 Inhibitor/0.9275 Non-inhibitor/0.9477 Inhibitor/0.5438 Non-inhibitor/0.8751 Non-inhibitor/0.8501 Non-inhibitor/0.6308 Non-inhibitor/0.6308 Non-inhibitor/0.8874 Non-inhibitor/0.8220

18

115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145.


+/0.9622 +/0.9622 +/0.7871 +/0.8180 +/0.9023 +/0.7359 +/0.9747 +/0.9460 -/0.6972 +/0.7766 +/0.7441 +/0.9727 -/0.7332 -/0.7324 -/0.8206 +/0.6481 +/0.6679 +/0.7948 +/0.8273 +/0.8696 +/0.8894 +/0.7145 +/0.7658 +/0.8045 +/0.8508 -/0.7893 +/0.8499 -/0.8026 -/0.8747 +/0.6481 -/0.5969

+/0.9962 +/0.9962 +/0.9950 -/0.8772 +/0.9956 +/0.9926 +/0.9817 +/0.9950 -/0.6384 +/0.9958 +/0.9904 +/1.0000 -/5345 +/0.7128 +/0.5718 +/1.0000 +/1.0000 +/0.9958 -/0.8590 -/0.9057 -/0.8847 +/0.9970 -/0.9725 +/0.9962 +/1.0000 +/0.7664 +/0.9827 -/0.6373 +/0.5519 +/1.0000 +/0.8122

+/0.6661 +/0.6661 -/0.5561 -/0.7416 -/0.6938 -/0.5788 -/0.5838 +/0.7107 -/0.7517 -/0.6579 +/0.7038 -/0.6348 -/0.6670 -/0.7715 -/0.7396 -/0.6213 +/0.7247 +/0.7377 -/0.7940 -/0.7010 -/0.6771 +/0.6976 -/0.7383 -/0.5600 -/0.5662 -/0.6805 +/0.7443 -/0.7762 -/0.6466 -/0.6213 -/0.5175

1.2748 1.2748 1.0507 -0.4171 0.9419 0.6232 0.4139 1.2877 0.1761 0.4746 1.2301 0.6010 0.2883 0.1522 -0.0245 0.6335 1.1454 1.1925 0.0248 -0.4691 -0.5304 0.8578 -0.8122 1.0681 1.0495 0.2644 0.9946 -0.0044 0.4197 0.6335 1.0331

Non-substrate/0.5098 Non-substrate/0.5098 Non-substrate/0.8712 Non-substrate/0.6824 Non-substrate/0.7675 Substrate/0.7258 Non-substrate/0.6996 Substrate/0.5439 Substrate/0.6128 Substrate/0.5430 Substrate/0.6060 Substrate/0.5115 Substrate/0.8135 Substrate/0.6504 Substrate/0.5952 Substrate/0.5139 Substrate/0.5317 Substrate/0.5507 Non-substrate/0.6991 Non-substrate/0.7469 Non-substrate/0.7616 Substrate/0.5193 Non-substrate/0.6204 Non-substrate/0.7702 Non-substrate/0.7781 Substrate/0.6067 Substrate/0.6237 Substrate/0.5799 Substrate/0.8572 Substrate/0.5139 Non-substrate/0.5489

Non-inhibitor/0.5630 Non-inhibitor/0.5630 Inhibitor/0.7151 Non-inhibitor/0.5763 Non-inhibitor/0.7835 Non-inhibitor/0.6162 Non-inhibitor/0.8203 Inhibitor/0.7565 Non-inhibitor/0.6451 Inhibitor/0.8462 Inhibitor/0.8618 Non-inhibitor/0.6811 Non-inhibitor/0.6540 Non-inhibitor/0.8464 Non-inhibitor/0.5739 Inhibitor/0.8904 Inhibitor/0.8995 Inhibitor/0.7262 Non-inhibitor/0.8811 Non-inhibitor/0.9899 Non-inhibitor/0.9949 Inhibitor/0.7713 Non-inhibitor/0.9611 Inhibitor/0.9100 Inhibitor/0.9301 Non-inhibitor/0.9559 Inhibitor/0.7310 Non-inhibitor/0.7076 Inhibitor/0.7646 Inhibitor/0.8904 Non-inhibitor/0.8674

19

146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174. 175. 176.


+/0.7397 -/0.8334 +/0.6975 -/0.5319 -/0.6721 +/0.8383 -/0.6083 +/0.8585 +/0.9172 -/0.5510 -/0.9676 +/0.7948 +/0.7624 +/0.7558 -/08688 -/0.5447 -/0.7339 +/0.6236 +/0.5759 -/0.9201 +/0.8803 +/0.5305 +/0.9386 +/0.8265 +/0.7406 -/0.5562 -/0.8301 +/0.9836 -/0.6457 -/0.6920 +/0.9567

+/1.0000 +/0.9631 +/1.0000 +/0.8467 -/0.6124 +/0.9951 -/0.5528 +/0.9962 +/0.8741 +/0.7027 -/0.7578 +/0.9958 +/0.9863 +/0.6037 +/0.6598 +/0.8809 -/0.6607 +/0.9456 +/0.9818 +/0.7215 +/1.0000 -/0.7539 +/0.9928 -/0.6831 +/0.9846 -/0.6563 -/0.5565 +/0.9970 +/0.9843 +/0.9739 +/0.9927

-/0.6366 -/0.6671 +/0.6872 -/0.6895 -/0.7743 -/0.5402 -/0.7339 +/0.8056 -/0.6151 -/0.7571 -/0.7193 +/0.7377 +/0.6724 -/0.8294 -/0.6274 -/0.6788 -/0.7818 -/0.6210 +/0.6426 -/0.6532 -/0.7012 -/0.8741 -/0.5443 -/0.5560 -/0.6459 -/0.7790 -/0.7671 -/0.6715 -/0.6299 -/0.6510 +/0.7049

0.7285 0.2557 1.0131 0.0453 0.1678 0.6540 0.0435 1.3087 0.1504 0.1007 0.4523 1.1925 1.0567 -0.7657 0.2530 0.6970 0.0609 0.8200 0.6834 0.3914 0.3273 -0.7338 1.0805 0.7247 0.6073 -0.0181 0.0515 0.8034 0.4626 0.3162 1.1249

Non-substrate/0.6246 Substrate/0.6693 Substrate/0.5392 Substrate/0.5899 Substrate/0.6707 Substrate/0.5581 Substrate/0.6812 Substrate/0.5441 Non-substrate/0.6509 Substrate/0.7339 Substrate/0.6598 Substrate/0.5281 Substrate/0.6550 Substrate/0.5687 Substrate/0.5429 Substrate/0.5689 Substrate/0.6913 Substrate/0.6246 Substrate/0.5899 Substrate/0.8799 Substrate/0.6652 Substrate/0.5598 Non-substrate/0.7687 Non-substrate/0.6157 Substrate/0.6783 Substrate/0.6852 Substrate/0.5761 Non-substrate/0.8247 Substrate/0.5653 Substrate/0.8612 Non-substrate/0.6459

Non-inhibitor/0.8077 Non-inhibitor/0.9054 Inhibitor/0.8362 Non-inhibitor/0.9527 Non-inhibitor/0.8530 Inhibitor/0.7959 Non-inhibitor/0.7663 Inhibitor/0.8590 Non-inhibitor/0.6820 Non-inhibitor/0.5318 Non-inhibitor/0.6433 Inhibitor/0.7262 Inhibitor/0.7731 Inhibitor/0.5426 Non-inhibitor/0.7138 Non-inhibitor/0.9570 Non-inhibitor/0.6550 Non-inhibitor/0.8328 Inhibitor/0.9361 Non-inhibitor/0.5294 Non-inhibitor/0.5501 Non-inhibitor/0.8511 Non-inhibitor/0.6456 Non-inhibitor/0.7681 Non-inhibitor/0.7422 Non-inhibitor/0.6637 Non-inhibitor/0.8751 Non-inhibitor/0.8220 Non-inhibitor/0.9069 Inhibitor/0.6073 Non-inhibitor/0.7215

20

177. 178. 179. 180. 181. 182. 183. 184. 185. 186. 187. 188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207.


+/0.7834 +/0.9179 +/0.9305 -/0.6442 +/0.9701 -/0.5139 +/0.9340 +/0.8847 +/0.7658 -/0.8742 -/0.5683 +/0.8572 -/0.6470 +/0.9193 +/0.9188 +/0.7711 -/0.6404 +/0.5799 +/0.5468 +/0.9504 +/0.8580 -/0.8261 +/0.8733 +/0.7835 +/0.6500 -/0.7724 +/0.8441 +/0.8372 -/0.6524 +/0.9454 -/0.6721

+/1.0000 -/0.8701 -/0.9016 +/0.8607 +/0.9745 -/0.6996 +/0.6146 +/1.0000 -/0.9725 +/0.5777 +/0.9834 +/0.9958 +/0.8755 +/0.9501 +/0.9841 +/0.9953 +/0.9534 +/0.9613 +/0.9903 +/0.9920 +/0.9974 +/0.6277 +/1.0000 +/0.9974 +/0.8803 +/0.9811 +/0.9822 +/1.0000 +/0.8474 +/0.9441 -/0.6124

-/0.6139 -/0.7487 -/0.7799 -/0.7172 +/0.5000 -/0.7877 +/0.5925 -/0.6508 -/0.7383 -/0.6465 -/0.5476 +/0.7635 -/0.5391 -/0.6800 +/0.6500 -/0.6766 -/0.8017 -/0.5303 +/0.5346 +/0.7129 -/0.5382 -/0.8272 -/0.7168 -/0.6839 -/0.6179 -/0.7001 +/0.6528 +/0.8512 -/0.658 -/0.5510 -/0.7743

0.9573 -0.4812 -0.1256 0.0260 0.7032 -0.0081 0.7642 0.7080 -0.8122 0.3226 0.9322 1.2859 0.8752 -0.0038 1.2280 0.1369 -0.1279 0.8450 0.8138 1.2800 1.1444 -0.6093 0.5706 -0.0306 0.7190 0.2760 0.9751 1.3827 0.4101 1.0793 0.1678

Substrate/0.8681 Non-substrate/0.6832 Non-substrate/0.7742 Substrate/0.5772 Non-substrate/0.8240 Substrate/0.7029 Substrate/0.5818 Substrate/0.6779 Non-substrate/0.6204 Substrate/0.8608 Substrate/0.6191 Substrate/0.5358 Substrate/0.6640 Non-substrate/0.5078 Substrate/0.6187 Substrate/0.5239 Substrate/0.7492 Substrate/0.5471 Non-substrate/0.5078 Non-substrate/0.6494 Non-substrate/0.7022 Substrate/0.7816 Substrate/0.6994 Non-substrate/0.5898 Non-substrate/0.5668 Substrate/0.8628 Non-substrate/0.5918 Non-substrate/0.5550 Substrate/0.6015 Non-substrate/0.7746 Substrate/0.6707

Inhibitor/0.6555 Non-inhibitor/0.9537 Non-inhibitor/0.9606 Non-inhibitor/0.9420 Non-inhibitor/0.9582 Non-inhibitor/0.7164 Non-inhibitor/0.6117 Inhibitor/0.5000 Non-inhibitor/0.9611 Inhibitor/0.6420 Non-inhibitor/0.6993 Inhibitor/0.8178 Non-inhibitor/0.8128 Non-inhibitor/0.9135 Inhibitor/0.5738 Non-inhibitor/0.8622 Non-inhibitor/0.8677 Inhibitor/0.5000 Inhibitor/0.9135 Non-inhibitor/0.5818 Inhibitor/0.8295 Non-inhibitor/0.9200 Non-inhibitor/0.5831 Non-inhibitor/0.8724 Inhibitor/0.5899 Non-inhibitor/0.5774 Inhibitor/0.5430 Inhibitor/0.9404 Non-inhibitor/0.8869 Non-inhibitor/0.8626 Non-inhibitor/0.8530

21

208. 209. 210. 211. 212. 213. 214. 215. 216. 217. 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238.


-/0.7067 -/0.6215 -/0.8793 -/0.7418 -/0.8895 -/0.8056 +/0.8923 +/0.5342 +/0.7224 +/0.5352 -/0.6083 +/0.9622 +/0.8247 +/0.9489 +/0.8527 +/0.7597 +/0.5884 +/0.5884 -/0.5512 +/0.5341 +/0.7092 +/0.8784 -/0.7896 +/0.9853 +/0.7757 -/0.7951 -/0.6706 +/0.9072 +/0.6693 +/0.5196 +/0.6145

+/0.7507 +/0.8779 +/0.6045 -/0.8209 +/0.5182 -/0.6590 +/0.9842 -/0.7342 +/0.9820 -/0.6347 -/0.5528 +/0.9962 +/0.7108 +/0.9921 +/0.9946 +/0.5691 +/0.9760 +/0.9760 +/0.6514 -/0.8558 +/0.9932 +/0.9490 +/0.9880 +/0.5085 +/0.9742 +/0.7473 +/0.5601 +/0.6146 +/0.9643 +/0.8801 +/0.9387

-/0.7584 -/0.6359 -/0.7366 -/0.8694 -/0.6237 -/0.7652 +/0.5948 -/0.7863 -/0.5352 -/0.7839 -/0.7339 +/0.6661 -/0.7557 +/0.6594 -/0.5972 -/0.7467 -/0.6690 -/0.6690 -/0.7701 -/0.8980 -/0.5772 -/0.5362 -/0.6371 -/0.6308 -/0.5632 -/0.6844 -/0.7053 +/0.6023 -/0.7042 -/0.6851 -/0.5763

-0.0719 0.4807 0.2500 -0.7314 0.9745 0.1081 1.0606 0.0357 0.9913 -0.0320 0.0435 1.2745 -0.0955 1.3208 0.8248 0.2150 0.0277 0.0277 -0.1191 -0.6447 0.8138 0.7564 0.5662 0.3319 1.2090 0.2600 0.1395 0.7455 0.3958 0.0263 1.0440

Substrate/0.6120 Substrate/0.5909 Substrate/0.6802 Substrate/0.6543 Substrate/0.8457 Substrate/0.5735 Substrate/0.6586 Substrate/0.5937 Substrate/0.6615 Substrate/0.7020 Substrate/0.6812 Non-substrate/0.5098 Non-substrate/0.5414 Substrate/0.5231 Substrate/0.6571 Substrate/0.5691 Substrate/0.5812 Substrate/0.5812 Substrate/0.6366 Substrate/0.5763 Non-substrate/0.6458 Substrate/0.8017 Non-substrate/0.5080 Non-substrate/0.8009 Non-substrate/0.635 Non-substrate/0.5566 Substrate/0.5651 Substrate/0.5619 Substrate/0.5323 Substrate/0.5890 Non-substrate/0.7357

Non-inhibitor/0.9389 Non-inhibitor/0.9146 Non-inhibitor/0.9021 Non-inhibitor/0.8980 Inhibitor/0.7599 Non-inhibitor/0.5633 Inhibitor/0.9627 Non-inhibitor/0.7749 Non-inhibitor/0.6914 Non-inhibitor/0.7470 Non-inhibitor/0.7663 Non-inhibitor/0.5630 Non-inhibitor/0.8112 Non-inhibitor/0.5174 Non-inhibitor/0.6796 Non-inhibitor/0.7684 Non-inhibitor/0.9811 Non-inhibitor/0.9811 Non-inhibitor/0.7446 Non-inhibitor/0.8279 Non-inhibitor/0.5236 Non-inhibitor/0.8135 Non-inhibitor/0.7293 Non-inhibitor/0.9749 Non-inhibitor/0.5910 Non-inhibitor/0.8707 Non-inhibitor/0.9156 Non-inhibitor/0.5704 Non-inhibitor/0.9757 Non-inhibitor/0.9667 Inhibitor/0.5932

22

239. 240. 241. 242. 243. 244. 245. 246. 247. 248. 249. 250. 251. 252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268. 269.


-/0.8710 +/0.7835 +/0.7948 +/0.9622 +/0.9504 -/0.5192 +/0.5192 -/0.8639 +/0.6999 +/0.8585 +/0.7207 -/0.8466 -/0.9102 +/0.8673 +/0.8050 +/0.8642 +/0.5963 +/0.9794 +/0.5084 +/0.9622 -/0.6594 -/0.8688 +/0.7591 +/0.8428 -/0.7494 -/0.5105 -/0.8735 +/0.8580 +/0.8986 +/0.8557 -/0.6524

+/0.8398 +/0.9974 +/0.9958 +/0.9962 +/0.9920 -/0.8970 +/0.7778 -/0.9128 +/1.0000 +/0.9962 +/1.0000 +/0.7164 -/0.7642 +/0.9968 +/0.9422 +/0.9903 +/0.7242 +/1.0000 +/0.9103 +/0.9962 +/0.6902 +/0.6598 +/1.0000 -/0.7914 -/0.7626 +/0.9706 +/0.9328 +/0.9974 -/0.8770 +/0.9710 +/0.8474

-/0.6863 -/0.6839 +/0.7377 +/0.6661 +/0.7129 -/0.8866 -/0.5772 -/0.8051 +/0.6905 +/0.5441 -/0.7114 -/0.6321 -/0.6464 -/0.5160 -/0.6450 +/0.7266 -/0.6514 +/0.5000 -/0.7087 +/0.6661 -/0.7121 -/0.6274 +/0.7338 -/0.7790 -/0.7253 -/0.7241 -/0.7569 -/0.5382 -/0.7581 -/0.6567 -/0.6015

0.2665 -0.0306 1.1925 1.2748 1.2800 -0.6098 0.5610 -0.7185 1.1374 1.3087 0.4081 0.3164 -0.3389 1.5008 0.6697 1.0187 0.2589 1.4499 0.3200 1.2748 0.0718 0.2530 1.1162 -0.3349 -0.5320 0.0638 0.3258 1.1444 -0.1852 0.5933 0.4101

Substrate/0.6939 Non-substrate/0.5898 Substrate/0.5507 Non-substrate/0.5098 Non-substrate/0.6494 Substrate/0.6828 Substrate/0.6904 Substrate/0.8148 Substrate/0.5169 Substrate/0.5441 Substrate/0.6574 Substrate/0.8526 Substrate/0.8441 Non-substrate/0.7141 Substrate/0.6433 Substrate/0.5150 Substrate/0.5613 Non-substrate/0.6597 Substrate/0.7647 Non-substrate/0.5098 Substrate/0.6353 Substrate/0.5429 Non-substrate/0.5197 Non-substrate/0.6461 Substrate/0.5595 Substrate/0.7733 Substrate/0.7702 Non-substrate/0.7022 Non-substrate/0.6461 Substrate/0.8210 Substrate/0.6015

Inhibitor/0.7826 Non-inhibitor/0.8724 Inhibitor/0.7262 Non-inhibitor/0.5630 Non-inhibitor/0.5818 Non-inhibitor/0.7947 Non-inhibitor/0.5881 Non-inhibitor/0.9285 Inhibitor/0.9048 Inhibitor/0.8590 Non-inhibitor/0.8122 Inhibitor/0.5462 Non-inhibitor/0.9690 Non-inhibitor/0.9211 Non-inhibitor/0.9180 Inhibitor/0.7859 Non-inhibitor/0.7985 Non-inhibitor/0.8175 Inhibitor/0.6192 Non-inhibitor/0.5630 Non-inhibitor/0.8952 Non-inhibitor/0.7138 Inhibitor/0.8770 Non-inhibitor/0.9321 Non-inhibitor/0.9724 Non-inhibitor/0.8823 Non-inhibitor/0.9478 Inhibitor/0.8295 Non-inhibitor/0.9321 Inhibitor/0.5279 Non-inhibitor/0.8869

23

270. 271. 272. 273. 274. 275. 276. 277. 278. 279. 280. 281. 282. 283. 284. 285. 286. 287. 288. 289. 290. 291. 292. 293. 294. 295. 296. 297. 298. 299. 300.


+/0.6975 +/0.8454 +/0.9517 +/0.9622 -/0.7351 +/0.7163 +/0.6436 -/0.9838 +/0.6416 +/0.8138 -/0.7907 -/0.5847 -/0.8386 -/0.6478 -/0.6706 +/0.7537 +/0.8536 +/0.6430 +/0.5966 +/0.7658 +/0.8614 +/0.9108 +/0.8206 -/0.5318 -/0.7161 +/0.7591 -/0.9834 -/0.9676 -/0.8712 -/0.7670 +/0.8253

+/1.0000 +/0.9949 +/0.9719 +/0.9962 -/0.6573 +/0.9378 +/0.9494 +/0.8212 -/0.5914 +/0.9639 +/0.6899 +/0.9970 -/0.5809 +/0.9087 +/0.5601 +/0.9965 +/0.9862 +/0.9974 -/0.8777 -/0.9725 -/0.6386 +/0.9879 +/0.9484 -/0.5363 -/0.5112 +/1.0000 -/0.8897 -/0.7578 +/0.9671 +/0.9017 +/0.8382

+/0.6872 +/0.5264 +/0.7044 +/0.6661 -/0.6843 -/0.6531 -/0.6474 -/.6784 -/0.7938 -/0.5440 -/0.9197 -/0.6225 -/0.7561 -/0.6462 -/0.7053 -/0.6835 +/0.7475 +/0.7338 -/0.7946 -/0.7383 -/0.5431 +/0.6375 -/0.6425 -/0.7355 -/0.7163 +/0.7338 -/0.7430 -/0.7193 -/0.5814 -/0.6682 -/0.5809

1.0131 0.9271 1.3213 1.2748 0.1144 0.9251 0.2236 0.2463 -0.2906 0.9048 -0.9052 0.1918 0.1627 0.2135 0.1395 0.0010 0.8877 1.1354 -0.4482 -0.8122 0.6473 1.1585 0.0966 -0.0478 0.1521 1.1162 -0.4375 -0.0560 0.6836 0.2788 0.5221

Substrate/0.5392 Substrate/0.5351 Non-substrate/0.5267 Non-substrate/0.5098 Substrate/0.8032 Non-substrate/0.6482 Substrate/0.5531 Substrate/0.6990 Non-substrate/0.5148 Non-substrate/0.5055 Substrate/0.6892 Non-substrate/0.5912 Substrate/0.5699 Substrate/0.5601 Substrate/0.5651 Non-substrate/0.5908 Substrate/0.5189 Substrate/0.5785 Substrate/0.5000 Non-substrate/0.6204 Non-substrate/0.5794 Substrate/0.6830 Non-substrate/0.6342 Substrate/0.5953 Substrate/0.5668 Non-substrate/0.5197 Substrate/0.9003 Substrate/0.6598 Substrate/0.8077 Substrate/0.5766 Substrate/0.8216

Inhibitor/0.8362 Non-inhibitor/0.9181 Inhibitor/0.7600 Non-inhibitor/0.5630 Non-inhibitor/0.6838 Non-inhibitor/0.6429 Non-inhibitor/0.9327 Non-inhibitor/0.6196 Non-inhibitor/0.8096 Inhibitor/0.5921 Non-inhibitor/0.7593 Non-inhibitor/0.9279 Non-inhibitor/0.9236 Non-inhibitor/0.9710 Non-inhibitor/0.9156 Non-inhibitor/0.8568 Inhibitor/0.6591 Inhibitor/0.8929 Non-inhibitor/0.8488 Non-inhibitor/0.9611 Non-inhibitor/0.8983 Inhibitor/0.7466 Non-inhibitor/0.9730 Non-inhibitor/0.8153 Non-inhibitor/0.8937 Inhibitor/0.8770 Non-inhibitor/0.5761 Non-inhibitor/0.6433 Inhibitor/0.9732 Inhibitor/0.9410 Inhibitor/0.9711

24

301. 302. 303. 304. 305. 306. 307. 308. 309. 310. 311. 312. 313. 314. 315. 316. 317. 318. 319. 320. 321. 322. 323. 324. 325. 326. 327. 328. 329. 330. 331.


+/0.8313 +/0.8977 +/0.7558 -/0.7678 -/0.8743 +/0.6067 -/0.5510 -/0.5985 -/0.5130 +/0.6591 +/0.7870 -/0.8799 +/0.7631 +/0.7809 -/0.8147 +/0.9193 -/0.5939 -/0.6465 +/0.8116 -/0.9821 -/0.5401 +/0.6649 +/0.6296 +/0.8425 +/0.8764 +/0.9648 -/0.5714 +/0.8864 +/0.8614 +/0.9477 +/0.8267

+/1.0000 +/0.5243 +/0.9698 -/0.5322 +/0.6180 +/0.9085 +/0.7027 +/0.6252 +/0.9958 +/0.8819 -/0.9569 +/0.6393 -/0.9544 +/1.0000 +/0.9902 +/0.9501 -/0.9524 +/0.9703 +/0.9852 -/0.9037 +/1.0000 +/0.9962 +/0.9231 +/0.9861 +/0.9906 +/0.9820 -/0.7828 +/0.9853 +/0.5787 +/0.9766 +/0.9944

-/0.6131 +/0.5825 -/0.6931 -/0.7743 -/0.7573 +/0.5318 -/0.7571 -/0.6860 -/0.5223 -/0.7229 -/0.8143 -/0.6235 -/0.7458 +/0.6979 -/0.6279 -/0.6800 -/0.8102 -/0.8255 +/0.6893 -/0.7317 -/0.6406 +/0.5193 -/0.8187 +/0.7258 -/0.5259 -/0.5341 -/0.7548 -/0.7406 +/0.5952 +/0.6330 +/0.6179

1.0873 0.7461 -0.0347 -0.0727 0.3124 0.9912 0.1007 0.2160 0.8574 0.2898 -0.1243 0.3687 -0.8833 0.9647 0.5706 -0.0038 -0.7511 -0.0479 1.0052 -0.4402 0.7026 1.3067 0.1721 1.0492 1.1554 1.1504 -0.0527 0.3669 0.6650 0.7339 1.2063

Substrate/0.8668 Substrate/0.5726 Non-substrate/0.5123 Substrate/0.5445 Substrate/0.6574 Non-substrate/0.7154 Substrate/0.7339 Substrate/0.7339 Non-substrate/0.6721 Substrate/0.6498 Non-substrate/0.7710 Substrate/0.5363 Non-substrate/0.5275 Non-substrate/0.5122 Substrate/0.5458 Non-substrate/0.5078 Substrate/0.6126 Substrate/0.5237 Non-substrate/0.5388 Substrate/0.9052 Substrate/0.6953 Substrate/0.6175 Non-substrate/0.5729 Substrate/0.5402 Non-substrate/0.5902 Non-substrate/0.7541 Substrate/0.9103 Substrate/0.5774 Substrate/0.5768 Non-substrate/0.6506 Substrate/0.5330

Inhibitor/0.5428 Inhibitor/0.5282 Non-inhibitor/0.9509 Non-inhibitor/0.6250 Non-inhibitor/0.6754 Inhibitor/0.5119 Non-inhibitor/0.5318 Non-inhibitor/0.5318 Inhibitor/0.6103 Non-inhibitor/0.5167 Non-inhibitor/0.9336 Non-inhibitor/0.5708 Non-inhibitor/0.9777 Inhibitor/0.8017 Non-inhibitor/0.8995 Non-inhibitor/0.9135 Non-inhibitor/0.9908 Non-inhibitor/0.6820 Non-inhibitor/0.7399 Inhibitor/0.5351 Non-inhibitor/0.5088 Non-inhibitor/0.5540 Non-inhibitor/0.9098 Inhibitor/0.7946 Inhibitor/0.8857 Non-inhibitor/0.6124 Non-inhibitor/0.6903 Non-inhibitor/0.6526 Inhibitor/0.5916 Non-inhibitor/0.6776 Inhibitor/0.9872

25

332. 333. 334. 335. 336. 337. 338. 339. 340. 341. 342.

ZINC15968056 ZINC20761262 ZINC02091508 ZINC04027376 ZINC08964851 ZINC01799169 ZINC02130322 ZINC85879954 ZINC08917927 ZINC08790313 ZINC04235228

-/0.7529 +/0.8978 -/0.6121 +/0.9143 +/0.8506 +/0.9143 -/0.6442 +/0.8506 -/0.6342 -/0.6641 +/0.9364

+/0.9627 +/1.0000 +/0.6589 +/0.9880 +/0.9484 +/0.9880 +/0.8607 +/0.9484 +/0.9211 +/0.7932 +/0.9950

-/0.6579 -/0.7446 -/0.7393 +/0.6977 -/0.6425 +/0.6977 -/0.7122 -/0.6425 -/0.6641 -/0.6340 -/0.5167

0.3748 0.0854 0.3355 1.2972 0.0966 1.2972 0.0260 0.0966 0.1523 0.4006 1.2136

Substrate/0.8512 Substrate/0.6466 Substrate/0.6400 Substrate/0.6831 Non-substrate/0.6342 Substrate/0.6831 Substrate/0.5772 Non-substrate/0.6342 Substrate/0.5561 Substrate/0.6315 Non-substrate/0.6298

Non-inhibitor/0.8872 Non-inhibitor/0.8853 Non-inhibitor/0.6058 Inhibitor/0.8725 Non-inhibitor/0.9730 Inhibitor/0.8725 Non-inhibitor/0.9420 Non-inhibitor/0.9730 Inhibitor/0.7482 Non-inhibitor/0.7242 Non-inhibitor/0.6480

26

Supplementary Table 3- in-silico metabolism profile obtained from admetSAR server for selected 340 compounds. Selected 27compounds with reference ligands are highlighted in bold. Sr. No. 1.

CYP-2C9 substrate/inhibitor Bromopyruvat None substrate/Noninhibitor 2. Nitropropionat None substrate/Noninhibitor 3. ZINC30725806 Non-substrate/Noninhibitor 4. ZINC56871207 Non-substrate/Noninhibitor 5. ZINC30725812 Non-substrate/Noninhibitor 6. ZINC30724164 Non-substrate/Noninhibitor 7. ZINC08215755 Non-substrate/Noninhibitor 8. ZINC16052058 Non-substrate/Noninhibitor 9. ZINC95618132 Non-substrate/Noninhibitor 10. ZINC15280332 Non-substrate/Noninhibitor 11. ZINC12402869 Non-substrate/Noninhibitor 12. ZINC32789745 Non-substrate/Noninhibitor 13. ZINC28957444 Non-substrate/Non-

Zinc ID

CYP-2D6 substrate/inhibitor Non-substrate/Noninhibitor

CYP-3A4 substrate/inhibitor Non-substrate/Noninhibitor

CYP-1A2 inhibitor Non-inhibitor

CYP-2C19 inhibitor Noninhibitor

CYP inhibitory promiscuity Low

Non-substrate/Noninhibitor


Non-inhibitor

Noninhibitor

Low

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-

Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate / Inhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High 27

14. ZINC18007499 15. ZINC95100378 16. ZINC53276076 17. ZINC08295117 18. ZINC08215530 19. ZINC13473520 20. ZINC08215662 21. ZINC68572914 22. ZINC60094177 23. ZINC18456332 24. ZINC03983911 25. ZINC30320675 26. ZINC15878789 27. ZINC08444972 28. ZINC06879053 29. ZINC08217391

inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate / Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Non-

inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-

Substrate/Noninhibitor Non-substrate / Inhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/ Inhibitor

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

High

Inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

High

Non-substrate/Noninhibitor Non-substrate/Non-

Inhibitor

Inhibitor

Low

Non-inhibitor

Non-inhibitor

Low 28


inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/ Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-


inhibitor Substrate/ Inhibitor

Non-inhibitor

Inhibitor

High

Substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Substrate/ Inhibitor

Non-inhibitor

Non-inhibitor

Low


Inhibitor

Inhibitor

High

Substrate/Noninhibitor Substrate/ Inhibitor

Inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High


Non-inhibitor

Inhibitor

High

Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Non-

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High 29

46. ZINC02129751 47. ZINC30320734 48. ZINC13508104 49. ZINC70712214 50. ZINC70712316 51. ZINC09435164 52. ZINC84758235 53. ZINC12405084 54. ZINC70704586 55. ZINC02128675 56. ZINC04293330 57. ZINC08215878 58. ZINC70686670 59. ZINC01783240 60. ZINC30320731

inhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor

inhibitor Non-substrate/Noninhibitor

inhibitor Substrate/Noninhibitor

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor

Non-inhibitor

Noninhibitor

Low

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High

Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

30


Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High

Inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Substrate/Noninhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Noninhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Noninhibitor

Low

Non-substrate/Noninhibitor Non-substrate/Noninhibitor

Substrate/Noninhibitor Substrate/Noninhibitor

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor

Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/ Inhibitor

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

Low

31


Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/ Inhibitor Non-substrate/Noninhibitor Non-substrate/ Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-


Non-inhibitor

Non-inhibitor

High

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/ Inhibitor Substrate/ Inhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Substrate/ Noninhibitor Non-substrate/Noninhibitor Substrate/ Inhibitor

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Substrate/ Noninhibitor Substrate/ Inhibitor

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

Low

Non-inhibitor

Inhibitor

High

Nonsubstrate/Inhibitor Substrate/ Noninhibitor

Non-inhibitor

Inhibitor

High

Non-inhibitor

Noninhibitor

Low

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

High

Nonsubstrate/Inhibitor Substrate/ Inhibitor

32


inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-


Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Substrate/ Noninhibitor Substrate/ Noninhibitor Substrate/ Noninhibitor Substrate/ Inhibitor

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High


Non-inhibitor

Inhibitor

High

Substrate/Noninhibitor Nonsubstrate/Inhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Substrate/ Inhibitor

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Non-inhibitor

Inhibitor

High

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Inhibitor

Non-inhibitor

High

Non-inhibitor

Non-inhibitor

High

Non-substrate/Non-

Non-inhibitor

Non-inhibitor

Low 33


inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Non-


inhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Substrate/Inhibitor

Inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Substrate/ Noninhibitor Substrate/ Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Inhibitor

Low

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Inhibitor

Non-inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Substrate/Non-

Non-inhibitor

Non-inhibitor

Low 34


inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-



Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Inhibitor

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Inhibitor

High 35


substrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Non-

inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor


Non-inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Substrate/Noninhibitor

Non-inhibitor

Noninhibitor

Low

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor

Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High

Substrate/Noninhibitor Nonsubstrate/Inhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

High

Nonsubstrate/Inhibitor Substrate/Noninhibitor Substrate/Noninhibitor

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Noninhibitor

Low

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-

Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate/Inhibitor

Inhibitor

Inhibitor

High

Non-inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High

Non-substrate/Non-

Non-inhibitor

Non-inhibitor

Low 36


inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/NonInhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-


inhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High


Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Nonsubstrate/Inhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

Low

Non-inhibitor

Non-inhibitor

High 37


inhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibito r Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Non-

inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Non-


Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Noninhibitor

Low


Non-inhibitor

Inhibitor

Low

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low


Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Noninhibitor

Low

Substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Inhibitor

Low

Inhibitor

Inhibitor

High

Non-substrate/Non-

Non-inhibitor

Non-inhibitor

Low 38


inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor

inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor


Inhibitor

Non-inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low


Non-inhibitor

Noninhibitor

Low

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor


Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Nonsubstrate/Inhibitor

Inhibitor

Inhibitor

High

39

201. ZINC29134440 202. ZINC08836808 203. ZINC02101321 204. ZINC96116434 205. ZINC70700093 206. ZINC30732502 207. ZINC02136499 208. ZINC02131604 209. ZINC09008170 210. ZINC02160798 211. ZINC04097715 212. ZINC35644633 213. ZINC02131286

Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibito r Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Nonsubstrate/Noninhibitor

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor


Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

High


Inhibitor

Inhibitor

Low


Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High


Inhibitor

Inhibitor

High

Non-inhibitor

Noninhibitor

Low



Non-inhibitor

Noninhibitor

Low



Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Noninhibitor

Low



Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Noninhibitor

Low



Non-inhibitor

Noninhibitor

Low

40


Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor



Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor

Inhibitor

Non-inhibitor

Low

Non-inhibitor

Noninhibitor

Low

Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High


Non-inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor

Inhibitor

Inhibitor

High

Inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

Low

Non-inhibitor

Noninhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Nonsubstrate/Inhibitor

41


Nonsubstrate/Noninhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor



Non-inhibitor

Noninhibitor

Low



Inhibitor

Inhibitor

Low

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor


Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Nonsubstrate/Inhibitor Substrate/Noninhibitor Nonsubstrate/Inhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

42


Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor


Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High


Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Non-

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-

Nonsubstrate/Inhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Nonsubstrate/Inhibitor Substrate/Inhibitor

Inhibitor

Inhibitor

High

Non-inhibitor

Inhibitor

High


Inhibitor

Non-inhibitor

High

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Non-

Non-inhibitor

Non-inhibitor

High

43


inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Non-

inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-


Inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High


Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High

Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Inhibitor

Inhibitor

High

Inhibitor

Non-inhibitor

High

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High

Substrate/Noninhibitor Substrate/Non-

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

44


inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-

inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor

inhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low


Non-inhibitor

Noninhibitor

Low

Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor


Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High


Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High


Non-inhibitor

Noninhibitor

Low

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-

Nonsubstrate/Inhibitor Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High 45


inhibitor Nonsubstrate/Inhibito r Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-

inhibitor Non-substrate/Noninhibitor

inhibitor Substrate/Noninhibitor

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Non-

Non-inhibitor

Inhibitor

Low

Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Nonsubstrate/Inhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Non-inhibitor

Inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Non-inhibitor

Noninhibitor

Low

Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Substrate/Non-

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-

Low 46


substrate/Inhibito r Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibito r Non-

inhibitor

inhibitor

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor

Substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Inhibitor

Non-substrate/Non-

inhibitor Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

High

Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Substrate/Noninhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-substrate/Noninhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

Low

Substrate/Non-

Non-inhibitor

Inhibitor

Low 47


substrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibito r

inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor


Inhibitor

Inhibitor

High

Substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Substrate/Inhibitor

Non-inhibitor

Non-inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High

Substrate/Noninhibitor Substrate/Noninhibitor Nonsubstrate/Inhibitor Substrate/Noninhibitor Non-substrate/Noninhibitor Substrate/Noninhibitor Substrate/Inhibitor

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

High

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Inhibitor

Inhibitor

High

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

High

Inhibitor

Inhibitor

Low

Nonsubstrate/Inhibitor Substrate/Noninhibitor Substrate/Noninhibitor

48

336. ZINC08964851 337. ZINC01799169 338. ZINC02130322 339. ZINC85879954 340. ZINC08917927 341. ZINC08790313 342. ZINC04235228

Non-substrate/Noninhibitor Nonsubstrate/Inhibito r Non-substrate/Noninhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor Non-substrate/Noninhibitor Nonsubstrate/Inhibitor



Non-inhibitor

Non-inhibitor

Low

Inhibitor

Inhibitor

Low

Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor Non-substrate/Noninhibitor


Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Non-inhibitor

Low

Non-inhibitor

Inhibitor

High

Substrate/Inhibitor

Inhibitor

Inhibitor

High


Non-inhibitor

Inhibitor

High

49

Supplementary Table 4: in-silico toxicity profile obtained from admetSAR server for selected 340 compounds.

Sr. No. 1.

ZINC ID

Carcinogen

hERG inhibtion

Biodegradation

Acute Oral Toxicity

Rat LD50

Bromopyruvate

AMES Toxicity Toxic

Carcinogens

Non -inhibitor

III/0.4234

2.8436

2.

Nitropropionate

Toxic

Carcinogens

Non -inhibitor

III/0.5286

2.3443

3.

ZINC30725806

Non-toxic

Non -inhibitor

III/0.5892

2.6241

4.

ZINC56871207

Non-toxic

III/0.5892

2.6241

5.

ZINC30725812

Non-toxic

III/0.5892

2.6241

6.

ZINC30724164

Non-toxic

III/0.5915

2.2229

7.

ZINC08215755

Non-toxic

III/0.5959

2.3856

8.

ZINC16052058

Non-toxic

III/0.5730

2.4356

9.

ZINC95618132

Non-toxic

III/0.6977

2.9583

10.

ZINC15280332

Non-toxic

III/0.5730

2.4356

11.

ZINC12402869

Non-toxic

III/0.6001

2.3100

12.

ZINC32789745

Non-toxic

III/0.5892

2.6241

13.

ZINC28957444

Non-toxic

III/0.5711

2.6308

14.

ZINC18007499

Non-toxic

Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Non-

Ready Biodegradable Ready Biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready

III/0.6032

2.5815

Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor

50

15.

ZINC95100378

Non-toxic

16.

ZINC53276076

Non-toxic

17.

ZINC08295117

Non-toxic

18.

ZINC08215530

Non-toxic

19.

ZINC13473520

Non-toxic

20.

ZINC08215662

Non-toxic

21.

ZINC68572914

Toxic

22.

ZINC60094177

Non-toxic

23.

ZINC18456332

Non-toxic

24.

ZINC03983911

Non-toxic

25.

ZINC30320675

Non-toxic

26.

ZINC15878789

Non-toxic

27.

ZINC08444972

Non-toxic

28.

ZINC06879053

Non-toxic

29.

ZINC08217391

Non-toxic

30.

ZINC70712237

Non-toxic

carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Non-

Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non -inhibitor

biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready

III/0.6223

2.5694

III/0.5855

2.5745

III/0.5490

2.3768

III/0.5984

2.0974

III/0.5567

2.3927

III/0.5825

2.3273

III/0.6092

2.2790

III/0.6789

2.3356

III/0.6048

2.2591

III/0.5855

2.5745

III/0.4416

2.9647

III/0.5730

2.4356

III/0.5939

2.3725

III/0.5267

2.4420

III/0.5730

2.4356

III/0.5899

2.4054 51

31.

ZINC13508937

Toxic

32.

ZINC68568879

Toxic

33.

ZINC77301904

Toxic

34.

ZINC12496167

Non-toxic

35.

ZINC08215481

Non-toxic

36.

ZINC24424495

Non-toxic

37.

ZINC04293328

Non-toxic

38.

ZINC03871961

Non-toxic

39.

ZINC70681081

Non-toxic

40.

ZINC02138703

Non-toxic

41.

ZINC95612014

Non-toxic

42.

ZINC08398287

Toxic

43.

ZINC02135897

Non-toxic

44.

ZINC68568482

Toxic

45.

ZINC02130997

Non-toxic

46.

ZINC02129751

Non-toxic


Non -inhibitor Non -inhibitor Inhibitor Non -inhibitor Non -inhibitor Non -inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor


III/0.6163

2.4932

III/0.5594

2.5101

III/0.5802

2.6762

III/0.5992

2.2543

III/0.6001

2.3100

III/0.5713

2.4375

III/0.6619

2.2815

IV/0.6113

2.0267

III/0.5619

2.9088

III/0.6968

2.5294

III/0.6964

2.3928

III/0.6366

2.3406

III/0.6889

2.6429

III/0.3950

3.5321

III/0.6483

2.6273

III/0.7209

2.2999 52

47.

ZINC30320734

Non-toxic

48.

ZINC13508104

Non-toxic

49.

ZINC70712214

Non-toxic

50.

ZINC70712316

Non-toxic

51.

ZINC09435164

Non-toxic

52.

ZINC84758235

Non-toxic

53.

ZINC12405084

Non-toxic

54.

ZINC70704586

Non-toxic

55.

ZINC02128675

Non-toxic

56.

ZINC04293330

Non-toxic

57.

ZINC08215878

Non-toxic

58.

ZINC70686670

Non-toxic

59.

ZINC01783240

Non-toxic

60.

ZINC30320731

Non-toxic

61.

ZINC96116329

Non-toxic

62.

ZINC02131176

Non-toxic

carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Non-

Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor


III/0.5607

2.7469

IV/0.4512

2.0047

III/0.5899

2.4054

III/0.5502

2.5462

III/0.4634

2.6407

III/0.6845

2.3901

III/0.5984

2.0974

III/0.6693

2.4716

III/0.6652

2.6748

III/0.4423

2.5403

III/0.5959

2.3856

III/5987

2.8036

III/0.6110

3.0005

III/0.5607

2.7469

III/0.5954

2.4987

III/0.6320

2.5551 53

63.

ZINC68601401

Non-toxic

64.

ZINC02131247

Non-toxic

65.

ZINC68572926

Toxic

66.

ZINC67913695

Non-toxic

67.

ZINC70686454

Non-toxic

68.

ZINC38143874

Non-toxic

69.

ZINC02109511

Non-toxic

70.

ZINC95913431

Non-toxic

71.

ZINC02137714

Non-toxic

72.

ZINC40308979

Toxic

73.

ZINC70706700

Non-toxic

74.

ZINC15521877

Non-toxic

75.

ZINC09519978

Toxic

76.

ZINC72324088

Non-toxic

77.

ZINC08215728

Non-toxic

78.

ZINC49538629

Toxic


Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor


III/0.5962

2.4473

III/0.6120

2.6005

III/0.5902

2.3552

III/0.3483

3.2895

III/0.4214

2.9119

III/0.7461

2.6027

III/0.6580

2.5784

III/0.6245

2.6133

III/0.5176

2.9663

III/0.6695

2.3584

III/0.6270

2.4727

III/0.6028

2.3549

III/0.5705

2.2887

III/0.5225

2.7656

III/0.5825

2.3273

III/0.3483

3.2895 54

79.

ZINC95100381

Toxic

80.

ZINC70681085

Non-toxic

81.

ZINC67912379

Toxic

82.

ZINC01307624

Non-toxic

83.

ZINC03872327

Non-toxic

84.

ZINC02129904

Non-toxic

85.

ZINC31165470

Non-toxic

86.

ZINC68563979

Toxic

87.

ZINC04292483

Non-toxic

carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Carcinogens

88.

ZINC04292484

Non-toxic

Carcinogens

Non-inhibitor

89.

ZINC02111081

Non-toxic

Non-inhibitor

90.

ZINC95100382

Toxic

91.

ZINC12883395

Non-toxic

92.

ZINC04292491

Non-toxic

Noncarcinogens Noncarcinogens Noncarcinogens Carcinogens

93.

ZINC04397091

Non-toxic

Non-inhibitor

94.

ZINC70699157

Non-toxic

Noncarcinogens Non-

Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor

Non-inhibitor Non-inhibitor Non-inhibitor

Non-inhibitor


III/0.6695

2.5038

III/0.5619

2.9088

III/0.6874

2.3092

III/0.6715

2.4614

III/0.6654

2.4124

II/0.4493

3.4720

III/0.7155

2.7346

III/0.6203

2.5280

III/0.4854

2.5361

III/0.4854

2.5591

III/0.5099

3.0334

III/0.6338

2.6109

III/0.6491

2.3861

III/0.4630

2.5735

III/0.5398

2.7422

III/0.6753

2.3502 55

95.

ZINC02133485

Non-toxic

96.

ZINC70707100

Non-toxic

97.

ZINC70686880

Toxic

98.

ZINC70664649

Toxic

99.

ZINC02134861

Non-toxic

100.

ZINC70686684

Non-toxic

101.

ZINC38152159

Toxic

102.

ZINC70670013

Non-toxic

103.

ZINC08917986

Non-toxic

104.

ZINC70686752

Non-toxic

105.

ZINC40312741

Toxic

106.

ZINC70707647

Non-toxic

107.

ZINC19850122

Non-toxic

108.

ZINC70705243

Non-toxic

109.

ZINC85875892

Non-toxic

110.

ZINC13403751

Toxic


Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Inhibitor Inhibitor Non-inhibitor


III/0.5500

2.9852

III/0.6796

2.3638

III/0.6062

2.4556

IV/0.4832

1.6815

III/0.6987

2.2778

III/0.4817

2.8356

III/0.5641

1.8214

III/0.7272

2.0612

III/0.6363

2.3760

III/0.4394

2.7514

III/0.6074

2.4554

III/0.6432

2.3643

III/0.5759

2.3238

III/0.6693

2.4716

III/0.6957

2.4235

III/0.5132

1.7227 56

111.

ZINC70664653

Toxic

112.

ZINC02137584

Non-toxic

113.

ZINC12880972

Non-toxic

114.

ZINC70664744

Non-toxic

115.

ZINC09422397

Toxic

116.

ZINC09421892

Toxic

117.

ZINC04292485

Non-toxic

118.

ZINC65731330

Non-toxic

119.

ZINC06142270

Toxic

120.

ZINC20111249

Non-toxic

121.

ZINC00517614

Non-toxic

122.

ZINC09184523

Non-toxic

123.

ZINC02161241

Non-toxic

124.

ZINC02149442

Non-toxic

125.

ZINC02129907

Non-toxic

126.

ZINC12296351

Toxic

carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Non-

Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor

biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready

IV/0.4832

1.6815

III/0.5321

2.9990

III/0.6363

2.4214

III/0.6319

1.9540

III/0.6650

2.8312

III/0.6650

2.8312

II/0.4267

2.5819

III/0.5132

2.6536

III.0.5813

1.7563

III/0.5738

2.5280

III/0.4892

1.5376

III/0.3975

2.8523

III/0.5081

2.9592

III/0.6910

2.4845

II/0.4493

3.4720

III/0.5753

2.4005 57

127.

ZINC70687434

Non-toxic

128.

ZINC02137968

Non-toxic

129.

ZINC70706734

Non-toxic

130.

ZINC12660614

Non-toxic

131.

ZINC70680868

Non-toxic

132.

ZINC11868922

Non-toxic

133.

ZINC12494956

Non-toxic

134.

ZINC16346988

Non-toxic

135.

ZINC13539741

Non-toxic

136.

ZINC00637197

Non-toxic

137.

ZINC30320773

Non-toxic

138.

ZINC04292705

Toxic

139.

ZINC03848924

Toxic

140.

ZINC02128678

Non-toxic

141.

ZINC02108084

Non-toxic

142.

ZINC02130359

Non-toxic


Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor


III/0.6067

2.4063

III/0.6933

2.5139

III/0.5493

2.7518

III/0.5150

2.7435

III/0.5619

2.9088

III/0.5012

2.8891

III/0.5375

2.3033

III/0.5787

2.3896

III/0.5357

2.3257

III/0.7098

2.5431

II/0.4476

2.9568

III/0.6168

2.6156

III/0.6389

2.5294

III/0.6652

2.6748

III/0.4793

2.8612

III/0.6212

2.7149 58

143.

ZINC70704625

Non-toxic

144.

ZINC12660617

Non-toxic

145.

ZINC68572923

Toxic

146.

ZINC43205655

Non-toxic

147.

ZINC70699624

Non-toxic

148.

ZINC11869021

Non-toxic

149.

ZINC02128421

Non-toxic

150.

ZINC02129752

Non-toxic

151.

ZINC02106366

Non-toxic

152.

ZINC02134700

Non-toxic

153.

ZINC11869881

Non-toxic

154.

ZINC08382326

Toxic

155.

ZINC02136654

Non-toxic

156.

ZINC04215267

Non-toxic

157.

ZINC11868946

Non-toxic

158.

ZINC08789743

Non-toxic


Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor


III/0.6690

2.4939

III/0.5150

2.7435

III/0.6216

2.3692

III/0.6662

2.4925

III/0.6347

2.3823

III/0.5987

2.8036

III/0.5383

3.0148

III/0.7209

2.2999

III/0.7480

2.4133

III/0.6462

2.6368

III/0.4033

2.6934

III/0.5967

2.5350

III/0.6031

2.7344

III/0.4523

1.8728

III/0.5012

2.8891

III/0.4991

3.3393 59

159.

ZINC67913699

Toxic

160.

ZINC08790466

Toxic

161.

ZINC02137586

Non-toxic

162.

ZINC02131248

Non-toxic

163.

ZINC85875799

Non-toxic

164.

ZINC14642116

Non-toxic

165.

ZINC70705931

Non-toxic

166.

ZINC32124284

Toxic

167.

ZINC77257057

Non-toxic

168.

ZINC03849002

Toxic

169.

ZINC68563983

Toxic

170.

ZINC15894185

Non-toxic

171.

ZINC02138358

Non-toxic

172.

ZINC02138465

Non-toxic

173.

ZINC70664749

Non-toxic

174.

ZINC70686697

Non-toxic


Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor


III/0.3483

3.2895

III/0.6466

2.5167

III/0.5321

2.9990

III/0.6120

2.6005

III/0.6472

2.4993

III/0.6270

2.8460

III/0.6923

2.5687

III/0.6695

2.3880

III/0.5246

1.6764

III/0.6992

2.2360

III/0.6203

2.5280

III/0.6217

2.4440

III/0.6201

2.6116

III/0.6459

2.5737

III/0.6319

1.9540

III/0.5723

2.5526 60

175.

ZINC70672938

Non-toxic

176.

ZINC09423047

Toxic

177.

ZINC15894157

Non-toxic

178.

ZINC12360703

Non-toxic

179.

ZINC19850119

Non-toxic

180.

ZINC02130321

Non-toxic

181.

ZINC95486411

Non-toxic

182.

ZINC02131178

Non-toxic

183.

ZINC70672395

Toxic

184.

ZINC12297086

Toxic

185.

ZINC08216005

Non-toxic

186.

ZINC70707316

Non-toxic

187.

ZINC95100383

Non-toxic

188.

ZINC02154588

Non-toxic

189.

ZINC36132220

Toxic

190.

ZINC08740529

Non-toxic


Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor


III/0.6873

2.5602

III/0.6187

2.6268

III/0.6076

2.9111

III/0.6048

2.2591

III/0.6165

2.1514

III/0.5006

2.9595

III/0.6466

2.2270

III/0.6320

2.5551

III/0.5557

3.2936

III/0.6261

2.4071

II/0.4476

2.9568

III/0.6881

2.4943

III/0.5727

2.5752

III/0.4209

2.8667

III/0.5955

2.5815

III/0.6312

2.3807 61

191.

ZINC02109489

Non-toxic

192.

ZINC02149301

Non-toxic

193.

ZINC29747667

Non-toxic

194.

ZINC08790278

Non-toxic

195.

ZINC71386351

Non-toxic

196.

ZINC09423957

Toxic

197.

ZINC04293322

Toxic

198.

ZINC67912196

Non-toxic

199.

ZINC20762813

Toxic

200.

ZINC02094539

Non-toxic

201.

ZINC29134440

Non-toxic

202.

ZINC08836808

Non-toxic

203.

ZINC02101321

Non-toxic

204.

ZINC96116434

Non-toxic

205.

ZINC70700093

Non-toxic

206.

ZINC30732502

Toxic


Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor


III/0.6580

2.5784

III/0.5923

2.3319

III/0.6001

2.2811

III/0.6622

2.5376

III/0.6973

2.3137

III/0.5503

2.6873

III/0.6746

2.3157

III/0.6449

2.8257

III/0.6792

2.2879

III/0.5840

2.3341

III/0.5909

2.4361

III/0.6760

2.5161

III/0.6117

2.3690

III/1.3827

2.4739

III/0.6451

2.5776

III/0.5646

2.7526 62

207.

ZINC02136499

Non-toxic

208.

ZINC02131604

Non-toxic

209.

ZINC09008170

Non-toxic

210.

ZINC02160798

Non-toxic

211.

ZINC04097715

Non-toxic

212.

ZINC35644633

Non-toxic

213.

ZINC02131286

Non-toxic

214.

ZINC02109431

Non-toxic

215.

ZINC02134863

Non-toxic

216.

ZINC08790352

Non-toxic

217.

ZINC02133096

Non-toxic

218.

ZINC02134701

Non-toxic

219.

ZINC09421943

Toxic

220.

ZINC02138974

Non-toxic

221.

ZINC28182553

Toxic

222.

ZINC85877614

Non-toxic




III/0.7209

2.2999

III/0.6638

2.4670

III/0.6290

2.4791

III/0.5941

2.7986

III/0.6011

2.2818

III/0.6788

2.6097

III/0.5989

2.7282

III/0.4400

2.9612

III/0.6987

2.2778

III/0.6371

2.4824

III/0.6454

2.4738

III/0.6462

2.6368

III/0.6650

2.8312

III/0.6540

2.3604

III/0.7297

2.8367

III/0.5783

2.5648 63

223.

ZINC02094401

Non-toxic

224.

ZINC08964840

Non-toxic

225.

ZINC08964839

Non-toxic

226.

ZINC02133043

Non-toxic

227.

ZINC04096316

Non-toxic

228.

ZINC08743310

Non-toxic

229.

ZINC08918120

Non-toxic

230.

ZINC01306071

Non-toxic

231.

ZINC13588931

Non-toxic

232.

ZINC70669955

Non-toxic

233.

ZINC20761515

Non-toxic

234.

ZINC02137669

Non-toxic

235.

ZINC70664694

Toxic

236.

ZINC03066102

Toxic

237.

ZINC02133487

Non-toxic

238.

ZINC08744271

Non-toxic




III/0.6963

2.2418

III/0.6471

2.3996

III/0.6471

2.3996

III/0.5517

2.7271

III/0.7395

2.7271

III/0.6866

2.1957

III/0.5528

2.6667

III/0.6377

2.4579

III/0.5448

2.5791

III/0.5748

2.2713

III/0.6091

2.2678

III/0.6757

2.6470

III/0.6201

3.0648

III/0.6541

2.0123

III/0.5500

2.9852

III/0.5748

2.4983 64

239.

ZINC20763335

Non-toxic

240.

ZINC02150161

Non-toxic

241.

ZINC11869206

Non-toxic

242.

ZINC09422377

Toxic

243.

ZINC09421979

Toxic

244.

ZINC14422056

Non-toxic

245.

ZINC68572159

Toxic

246.

ZINC67912546

Toxic

247.

ZINC02107555

Non-toxic

248.

ZINC08917829

Non-toxic

249.

ZINC40310142

Toxic

250.

ZINC70704879

Non-toxic

251.

ZINC14090000

Non-toxic

252.

ZINC12504487

Non-toxic

253.

ZINC85879767

Non-toxic

254.

ZINC11868978

Non-toxic


Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor


III/0.5998

2.5876

III/0.5840

2.3341

III/0.5012

2.8891

III/0.6650

2.8312

III/0.5503

2.6873

III/0.6749

2.5376

III/0.5934

2.6592

III/0.5062

3.0328

III/0.4902

2.7273

III/0.4033

2.6934

III/0.6347

2.2899

III/0.7081

2.4105

III/0.5156

2.2818

III/0.5276

2.3626

III/0.6818

2.4498

III/0.4817

2.8356 65

255.

ZINC12883683

Non-toxic

256.

ZINC0209440

Non-toxic

257.

ZINC12661702

Non-toxic

258.

ZINC09422944

Toxic

259.

ZINC02138561

Non-toxic

260.

ZINC12884457

Toxic

261.

ZINC70686632

Non-toxic

262.

ZINC20233084

Non-toxic

263.

ZINC26498948

Non-toxic

264.

ZINC70701473

Non-toxic

265.

ZINC70704524

Non-toxic

266.

ZINC04293318

Toxic

267.

ZINC08216074

Non-toxic

268.

ZINC01494900

Non-toxic

269.

ZINC70699959

Non-toxic

270.

ZINC11869019

Non-toxic

carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Non-

Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor


III/0.6676

2.3108

III/0.5592

2.3707

III/0.6791

2.3301

III/0.6650

2.8312

III/0.5783

2.7874

III/0.6466

2.5167

II/0.3801

2.8473

III/0.5944

2.0527

III/0.4657

2.0121

III/0.6505

2.4676

III/0.6301

2.5171

III/0.6746

2.3157

III/0.5825

2.2114

III/0.5689

2.6706

III/0.6451

2.5776

III/0.5987

2.8036 66

271.

ZINC68572912

Non-toxic

272.

ZINC02353184

Toxic

273.

ZINC09422709

Toxic

274.

ZINC70687058

Non-toxic

275.

ZINC79204240

Toxic

276.

ZINC02129853

Non-toxic

277.

ZINC04097459

Non-toxic

278.

ZINC02134917

Non-toxic

279.

ZINC68586043

Toxic

280.

ZINC67903526

Non-toxic

281.

ZINC02095190

Non-toxic

282.

ZINC02126939

Non-toxic

283.

ZINC02096971

Non-toxic

284.

ZINC02137671

Non-toxic

285.

ZINC02148180

Non-toxic

286.

ZINC11869195

Non-toxic


Inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor


III/0.9271

2.4101

III/0.7700

2.4885

III/0.6650

2.8312

III/0.6031

2.3964

III/0.6594

2.1938

III/0.5711

2.8642

IV/0.6091

1.7391

III/0.6352

2.4275

III/0.7016

2.5738

III/0.4775

2.5904

III/0.5865

2.4266

III/0.6260

2.5897

III/0.5558

2.5634

III/0.6757

2.6470

III/0.5839

2.3977

III/0.4479

2.7502 67

287.

ZINC02667118

Non-toxic

288.

ZINC04098737

Toxic

289.

ZINC16051708

Non-toxic

290.

ZINC13402517

Toxic

291.

ZINC04262881

Non-toxic

292.

ZINC85879957

Toxic

293.

ZINC02136786

Non-toxic

294.

ZINC02129026

Non-toxic

295.

ZINC70680964

Non-toxic

296.

ZINC08917782

Non-toxic

297.

ZINC11616463

Non-toxic

298.

ZINC38144858

Non-toxic

299.

ZINC12662687

Toxic

300.

ZINC70671818

Toxic

301.

ZINC35485252

Non-toxic

302.

ZINC79209975

Toxic

carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Non-

Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Inhibitor Inhibitor Inhibitor Non-inhibitor Non-inhibitor


III/0.7107

2.7984

III/0.7528

2.3482

II/0.4476

2.9568

III/0.5283

2.6766

III/0.6525

2.6540

III/0.6063

2.4543

III/0.5765

2.7877

III/0.6547

2.7123

II/0.3801

2.8473

III/0.5731

2.6630

III/0.4523

1.8728

III/0.6338

2.6827

III/0.6300

2.5641

III/0.6654

2.5611

III/0.5985

2.9205

III/0.5915

3.2114 68

303.

ZINC09317485

Non-toxic

304.

ZINC02116527

Non-toxic

305.

ZINC02160785

Non-toxic

306.

ZINC68563112

Non-toxic

307.

ZINC02136649

Non-toxic

308.

ZINC70700082

Non-toxic

309.

ZINC04265841

Toxic

310.

ZINC11866792

Non-toxic

311.

ZINC19796107

Non-toxic

312.

ZINC08876746

Non-toxic

313.

ZINC24809680

Non-toxic

314.

ZINC12662395

Non-toxic

315.

ZINC09597101

Non-toxic

316.

ZINC08740528

Non-toxic

317.

ZINC39817543

Non-toxic

318.

ZINC70672524

Non-toxic

carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Non-

Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor


III/0.6765

2.2843

III/0.6239

2.3746

III/0.6754

2.6313

III/0.6505

2.5708

III/0.6031

2.7344

III/0.6026

2.4017

III/0.6508

2.3852

III/0.6032

2.6458

III/0.5916

2.1419

III/0.6282

2.5215

III/0.4416

2.9647

III/0.4394

2.7514

III/0.6715

2.4614

III/0.6312

2.3807

III/0.6504

2.2076

III/0.6553

2.3458 69

319.

ZINC00639081

Non-toxic

320.

ZINC35807042

Non-toxic

321.

ZINC12296661

Non-toxic

322.

ZINC32501412

Non-toxic

323.

ZINC70669991

Non-toxic

324.

ZINC09054245

Non-toxic

325.

ZINC13570185

Non-toxic

326.

ZINC08872080

Toxic

327.

ZINC08790811

Non-toxic

328.

ZINC02149310

Non-toxic

329.

ZINC70672456

Toxic

330.

ZINC08647945

Non-toxic

331.

ZINC03071741

Non-toxic

332.

ZINC15968056

Non-toxic

333.

ZINC20761262

Toxic

334.

ZINC02091508

Non-toxic


Non-inhibitor Inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Inhibitor Non-inhibitor Non-inhibitor


III/0.6990

2.5750

III/0.5771

2.6033

III/0.6153

2.4129

III/0.6084

2.6201

III/0.5698

1.9990

III/0.6588

2.5597

III/0.6466

2.2404

III/0.6420

2.5355

III/0.7018

2.4472

III/0.6715

2.3208

III/0.6356

2.9619

III/0.6794

1.7707

III/0.4824

3.1770

III/0.6710

2.5023

III/0.6354

2.3247

III/0.6907

2.4156 70

335.

ZINC04027376

Non-toxic

336.

ZINC08964851

Toxic

337.

ZINC01799169

Non-toxic

338.

ZINC02130322

Non-toxic

339.

ZINC85879954

Toxic

340.

ZINC08917927

Non-toxic

341.

ZINC08790313

Non-toxic

342.

ZINC04235228

Non-toxic

carcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens Noncarcinogens

Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor Non-inhibitor

biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable Not ready biodegradable

III/0.6404

2.6314

III/0.6063

2.4543

III/0.6404

2.6314

III/0.5006

2.9595

III/0.6063

2.4543

III/0.6009

2.5052

III/0.6585

2.4579

III/0.6862

2.3677

71

Supplementary Table 5- Summary of docking energy and interacting residues of the top 27 compounds obtained from virtual screening and molecular docking studies by Autodock Tools, Autodock Vina and Molegro Virtual Docker. Residues involved in hydrogen bonding were highlighted in bold as well as selected hits for MDS is also highlighted in bold. Sr.N Compound o ID

Bindi IC50 ng Energ y Auto dock Kcal. mol-1 1. Bromopyruv -3.88 1.44 ate mM

Hbon d

5

Gly192,Ser191,Trp93, Leu348,Thr347,Ser31 7,Ser315,Asn313,His1 93

2. Nitropropio nate

-3.49

2.78 mM

8

3. ZINC639081

-5.99

40.35 µM

3

Residues

Binding Energy Autodoc k Vina

No. Residues of H. Bon d

(Kcal.m ol-1) -5.3

5

Gly192,His193,Arg22 8,Asn313,Ser315,Ser3 17,Thr347, Ser315, Asp108, Lys189

-5.7

9

Gly192, Arg228, His352, Asp153, Thr347, Leu348, Phe351, Trp93, Asp108, His193,

-7.0

7

MolDoc k Score MVD

No. of H. Bo nd

Gly192,Ser191,T -64.4181 5 rp93,Leu348,Thr 347,Tyr89,Ser315 ,Asn313,Trp283, Glu285,His193,A rg228 Gly192,His193,A -75.5476 10 rg228,Asn313,Se r315,Ser317,Thr 347,Glu285,Ser1 91,Asp108 Ser191,Gly192,A -160.846 6 rg228,His352,His 193,Asn313,Ser3 15,Ser317,Thr347 ,Leu348,Phe351,

Residues

Arg228,Gly192,Se r191,Trp93,Leu34 8,Thr347,Ser317, Pro316,Ser315,As n313,Glu285,His1 93 Trp93,Asp108,Lys 189,Ser191,Gly19 2,His193,Arg228, Trp283,Glu285,Se r315,Pro316,Ser31 7,Thr347,Leu348, Trp93,Asp108,Ser 191,Gly192,Arg22 8,Glu285,Trp283, Asn313,Phe345,Hi s193,Asn313,Ser3 72

Lys189

Trp93,Asp153,As p108,Leu194

4. ZINC130607 -6.91 1

8.59 µM

2

Ser191, Thr347, Arg228, Glu285, Asn313, Ser191, Gly192, His193, Ser315, Ser317, His352, Leu348, Trp93, Gly92, Ser91, Tyr89, Asp153

-7.4

8

Ser91,Trp93,Ser 191,Ser315,Ser3 17,Ser191,Arg22 8,Glu285,Tyr89, Leu348,His352,P he351,Asp153

-163.162 4

5. ZINC179916 9

-6.61

14.21 µM

4

6

Ser191,His193,A rg228,Ser315,Se r315,Ser317,Thr 347,His352,Leu3 48,Trp93,Asp153 ,Asp108,Lys189, Leu194

-158.639 6

6. ZINC210132 1

-6.94

8.13 µM

6

Ser191, His193, -6.9 Arg228, His352, Glu285, Tyr89, Asn313, Thr347, Ser315, Leu348, Ser317, Phe351, Trp93, Asp108, His193, Leu194, Asp108, Ser191, -6.9 Gly192, Arg228, Glu285, Asp153, His193, Leu194, Trp93, Ser317, Thr347, Leu348, Ser315,

5

Ser191,Gly192,A -164.342 5 rg228,Leu194,Hi s193,Ser317,Asn 313,His352,Leu3 48,Tyr89,Phe351, Trp93,Asp108,As

15,Thr347,Tyr89,L eu348,Ser91,Trp93 ,Asp153,Pro107,A sp108,Lys189 Ser91,Trp93,Asp1 08,Ser191,Glu182, Arg228,Glu285,Tr p283,His193,His18 0,Asn313,Ser315,P he345,Ser317,Thr3 47,Tyr89,Leu348,S er91,Trp93,Asp15 3,Asp108,Glu155, Lys189, Tyr89,Ser91,Gly1 92,Arg228,Asn31 3,Thr347,Trp283, His193,Ser315,Phe 345,Ser317,Pro316 ,Leu348,Tyr89,Trp 93,Asp153,Asp108 ,Pro107,Lys189 Ser91,Trp93,Asp1 08,Ser191,His180, Arg228,Trp283,As n313,Phe345,Ser3 15,Ser317,Thr347, Leu348,Tyr89,Pro

73

Asn313, Asp153

p153

7. ZINC210948 9

-5.34

120.94 µM

3

Trp93, Ser191, His352, Leu194, Ser317, Leu348, Phe351, Thr105, Asp108

-5.5

6

8. ZINC210951 1

-6.52

16.66 µM

3

Gly192, His193, Thr347, Arg228, Asn313, Leu348, Phe351, His352, Trp93, Ser317, Ser191, Leu194

-6.4

5

9. ZINC211108 -6.67 1

12.96 µM

3

Asp108, Ser317, His352, Ser191, His193, Leu194, Phe351, Leu348, Trp93, Thr105

-8.7

11

Ser191,Gly192,A -168.223 4 rg228,Asn313,Gl u285,Trp283,Tyr 89,Thr347,Ser315 ,Pro316,Ser317,H is352,Phe351,Trp 93,Leu194 Ser191,Gly192,A -172.155 8 rg228,His193,Le u194,Glu285,Asn 313,Ser315,Thr34 7,Leu348,His352, Phe351,Trp93,As p153

Tyr89,Ser91,Gly -168.859 11 92,Asn313,Ser31 5,Ser317,Thr347 ,His193,Ser191,A rg228,Trp283,His 180,Asp153,Thr3 47,Leu348,Trp93,

107,Asp108,Asp15 3,Glu155,Lys189, His180,Glu182 Ser191,Arg228,As n313,His193,Leu1 94,Glu285,Asn313 ,Ser315,Thr347,Le u348,His352,Phe3 51,Trp93,Asp153 Arg228,Glu285,Tr p283,His193,Asn3 13,Ser315,Ser317, Phe345,Thr347,Ty r89,Leu348,Ser91, Trp93,Asp15,Pro1 07,Glu155,Gln109, Lys189,Gln184,Hi s180,Ser191,Asp1 08, Tyr89,Ser91,Gly9 2,Asn313,Ser315, Ser317,Thr347,Hi s193,Trp283,Glu2 85,His193,Phe318, Asn319,His352,Le u348,Tyr89,Gln94, Trp93,Asp153,His

74

10. ZINC212975 1

-5.41

109.12 µM

3

Trp93, Asp108, His352, Leu194, Ser317, Phe351, His352, Leu348, Pro107

-6.1

2

Asp108,Ser191,L -179.364 9 eu194,Ser317,His 352,Phe351,Trp9 3,Thr105

11. ZINC212975 2

-5.43

104.24µ 1 M

Trp93, Ser191, Leu194, Ser317, His352, Thr105, Pro107, Asp108, Gln109

-5.9

3

Trp93,Ser317,Ty -167.326 8 r106,Leu194,Phe 351,Pro107

12. ZINC213035 9

-5.11

180.02 µM

2

Asp108, Ser317, Ser191, Leu194, His193, Leu348, Phe351, Asn355, Thr105, Pro107, Gln109

-6.3

8

Tyr89,Ser91,Gly -160.504 10 92,Ser191,Ser31 5,Thr347,Glu285 ,Ser91,Arg228,Tr p283,Asp153,Leu 348,Trp93,His19 3,Ser317,Pro316

13. ZINC213128 6

-5.29

132.1 µM

3

Gln333, Ala349, Lys334, Phe332,

-5.4

11

Trp93,Ser191,Hi -164.225 9 s193,Arg228,Asn

180,Arg228, His193,Arg228,As n313,Ser315,Ser3 17,Thr347,Glu182 ,His180,Trp283,Pr o316,His352,Leu3 48,Phe351,Trp93,T yr89,Ser91,Asp153 ,His180, Lys189,Asn313,Se r315,Ser317,Thr3 47,Ser91,His193, Glu182,Arg228,Gl u285,Pro316,His35 2,Leu348,Tyr89,Tr p93,Asp153,Asp10 8,Glu155, Ser191,His193,Ar g228,Asn313,Ser3 15,Ser317,Thr347 ,Tyr89,Trp283,Pro 316,His352,Phe35 1,Leu348,Thr347, Trp93,Ser91,Asp1 08,Asp153,His180, Lys189,Glu182 His193,Arg228,As n313,Ser315,Ser3 75

Trp320, Pro316, His352, Ala353, Ile346, Asn67

313,Ser315,Thr3 47,Tyr89,Leu194 ,Asp108,Lys189, Ser91,Asp153

14. ZINC213160 4

-4.92

247.27 µM

4

Trp93, Ser191, His352, Tyr106, Leu194, Pro316, Ser317, Phe351, Leu348, Thr105,

-5.0

11

Trp93,Ser191,Hi -166.643 10 s193,Arg228,Asn 313,Ser315,Ser3 17,Thr347,Tyr89 ,Pro316,Leu348,S er91,Asp153,Lys 189,Asp108

15. ZINC213304 3

-5.14

170.45 µM

2

Trp93, Ser191, Leu194, His193, Ser317, His352, Leu348

-6.0

5

Trp93,Ser191,Se r317,His193,Leu 194,His352

-156.184 8

16. ZINC213486 3

-5.91

91.1 µM

4

Trp93, Asp108, Ser191, Leu194, Ser317, His352, Thr105

-6.7

Ser191, Leu194, Ser317, Leu348, Phe351, Trp93, Thr105

-151.73

10

17,Thr347,Glu182 ,His180,Trp283,Pr o316,Leu348,Tyr1 89,Ser91,Trp93,As p153,His180,Asp1 08,Pro107,Lys189, Ser191,His193,Ar g228,Asn313,Ser3 15,Ser317,Thr347 ,Glu182,Gln184,Tr p283,Pro316,His35 2,Phe351,Leu348, Trp93,Gln94,Tyr8 9,Asp108,Asp153, His180,Lys189 Ser91,Trp93,His1 93,Ser315,Ser317, Thr347,His180,Ar g228,Glu285,Trp2 83,Phe345,Asn313 ,Pro316,His352,Ph e351,Gln94,Trp93, Tyr89,Asp108,Asp 153, Lys189,Ser191,Hi s193,Asn313,Ser3 15,Ser317,Ser91, Glu182,His180,Ar

76

17. ZINC213491 -7.41 7

3.69 µM

5

Trp93, Ser191, Ser317, Pro316, Arg228, Asp153, Tyr89, Ser91, Thr347, Leu348, His352, Asn313, His193, Leu194, Glu285

-7.4

5

Tyr89,Ser91,Asp -167.029 5 108,Ser317,His3 52,Glu285,Arg22 8,Asp153,Thr347 ,Leu348,Trp93,Hi s193,Leu194,Ser1 91

18. ZINC213649 9

-5.18

158.29 µM

2

Trp93, Ser191, Ser317, Leu194, His352, Phe351, Thr105, Pro107, Asp108

-6.5

8

Tyr89,Ser91,Trp -169.488 10 93,Ser191,Ser31 5,Thr347,Glu285 ,Ser91,His193,Ar g228,Trp283,Asp 153,His352,Pro31 6,Ser317

19. ZINC213767 1

-5.09

185.83 µM

2

Gln333, Ile329, Lys334, Phe332, Cys314, Ile346, His352, Pro316, Trp320

-5.5

6

Trp93,Lys189,Gl -164.733 7 y192,His193,Ser 317,His352,Asp1 53,Glu182,Arg22 8,Tyr89,Ser91,Th r347,Leu348,Ser3 15,Asp153

g228,Pro316,Leu3 48,Tyr89,Thr347,P he351,Trp93,Asp1 53,Glu155 Tyr89,Ser91,Trp9 3,Ser317,His352, Arg228,Glu285,Tr p283,Asn313,His1 93,Phe345,Ser315, Thr347,Tyr89,Phe 351,Asp108,Asp15 3, His193,Arg228,As n313,Ser315,Ser3 17,Thr347,Tyr89, Glu182,His180,Th r286,His193,Pro31 6,Leu348,His352,P he351,Ser91,Asp1 53,His180,Asp108, Pro107,Lys189 Trp93,Asp189,Ly s189,Gly192,His1 93,Arg228,Ser317 ,Trp283,Asn313,Se r315,Phe345,Pro31 6,His352,Leu348,T hr347,Phe351,Tyr8

77

20. ZINC213846 5

-7.21

5.18 µM

2

Trp93, His193, Glu285, Arg228, Trp283, His180, Asp153, Tyr89, Thr347, Leu348, His352, Ser317, Leu194, Ser191

-5.1

11

Trp93,Ser191,Hi -165.827 11 s193,Arg228,Asn 313,Ser315,Ser3 17,Thr347,Tyr89 ,Lys189,Asp153, Ser91,Leu348,Ph e351,His352,Asp 108,Lys189

21. ZINC216078 5

-4.44

558.7 µM

3

Trp93, Asp108, Ser191, Leu194, Ser317, His352, Phe351,

-5.9

10

22. ZINC216079 8

-5.18

160.82 µM

2

Asp108, Ser317, Leu194, Leu348, His352, Phe351, Asn335, Thr105, Trp93, Pro107

-5.6

10

Tyr89,Ser91,Gly -172.627 9 92,Ser191,His19 3,Ser315,Ser317, Thr347,Arg228, Trp283,Asn313,S er315,Pro316,Leu 348,His352,Phe3 51,Trp93 His193,Arg228, -147.063 8 Asn313,Ser315,S er317,Thr347,Ty r89,Lys189,Ser19 1,Leu194,Leu348 ,Ser91,Asp153,Tr p93,Asp108,

9,Ser91,Asp153,As p108,Glu182,Ser1 91 Ser191,His193,Ar g228,Asn313,Ser3 15,Ser317,Thr347 ,His152,Lys189,Gl u182,His180,Trp2 83,Leu348,Tyr89,P he351,Ser91,Trp93 ,Asp153,His180,A sp108, His193,Arg228,As n313,Ser315,Ser3 17,Thr347,Gln184 ,Glu182,His180,Tr p283,Pro316,Tyr8 9,Leu348,Trp93,Se r91,Asp153,Asp10 8,Pro107,Lys189 Asp108,Ser191,Hi s193,Arg228,Asn3 13,Ser315,Thr347 ,His180,Glu285,Se r317,Pro316,Leu34 8,Ser91,Trp93,Pro 107,Asp108,Glu15 5,Asp153,Lys189,

78

23. ZINC213771 4

-5.6

78.62 µM

2

Trp93, Asp108, His193, Ser317, Phe351, Thr105, Pro107, Ser191

-5.1

7

24. ZINC402737 6

-5.01

211.72 µM

3

Ser191, Ser317, -4.7 His352, Leu194, Leu348, Phe351, Thr105, Trp93, Asp108

4

25. ZINC426288 1

-6.78

10.75 µM

3

His193, Ser317, His352, Arg228, Trp283, Asn313, Asp153, Tyr89, Thr347, Leu348, Phe351,Trp93, Ser91, Ser191, Gly192

3

-5.3

Tyr89,Ser91,Gly -153.5 10 92,Ser315,Thr34 7,Glu285,Ser91, Trp283,Arg228,H is193,Ser191,Asn 313,Ser317,Pro31 6,Phe351,His352, Leu348,Trp93,As p153 His193,Arg228,S -161.794 5 er315,Ser317,As p153,Ser91,Tyr89 ,Glu285,Leu348, His193,Leu194,T rp93,Ser191,Asp1 08,Lys189

Asp108,Ser191, -161.767 8 His193,Arg228,G lu285,Leu194,As n313,Ser317,Thr3 47,Leu348,Trp93

Glu182,Gln184 Ser191,His193,Ar g228,Asn313,Ser3 15,Ser317,Thr347 ,Tyr89,Glu182,His 180,Trp283,Pro31 6,Leu348,His352,P he351,Ser91,Trp93 ,Asp153,Asp108,L ys189 Trp93,His193,Arg 228,Ser315,Thr34 7,Glu182,Glu285, Trp283,Asn313,Se r317,Pro316,His35 2,Leu348,Tyr89,Se r91,Trp93,Asp153, Asp108,Glu155,Ly s189 Tyr89,Ser91,Trp9 3,Lys189,Ser191, His193,Glu182,Gl n184,Arg182,Glu2 85,Trp283,His180, His193,Asn313,Se r317,Thr347,Leu3 48,Trp93,Pro107,A sp108,Leu194,Glu

79

26. ZINC891812 0

-6.5

23.42 µM

2

Trp93, Asp108, Leu194, Ser317, Phe351, Asn355, Thr105, Pro107, Asp108

-5.0

1

Ser317, Phe351,His352,T rp93,Leu194

-163.12

27. ZINC354852 52

-5.59

79.43 µM

1

Trp93, Ser191, Leu194, Ser317, His352, Phe351, Leu348, Pro107, Asp108

-6.5

1

Trp93, Arg228, Asp153, Ser315, Thr347, Leu348, Ser317, Asp108, Ser191, Leu194, His193,

-161.353 5

28. ZINC356446 33

-3.78

1.71 mM

1

Leu348, Phe351, His352, Thr105, Pro107, Asp108, Trp93, Ser317

-6.3

5

Tyr89,Ser91,Trp -163.885 5 93,Arg228,His35 2,Lys189,Ser191, His193,Leu194,P ro316,Ser317,Thr 347,Leu348,Trp9 3,Asp153,Arg228

6

155 Trp93,Asn313,Ser 315,Ser317,Ser19 1,His180,Arg228, Glu285,Trp283,Hi s193,Phe345,Pro31 6,Thr347,Tyr89,Hi s352,Leu348,Ser91 ,Pro107,Asp108,A sp153,Lys189 Ser191,Gly192,Hi s193,Ser91,Glu18 2,Leu194,Arg228, Glu185,Trp283,As n313,Ser315,Phe3 45,Ser317,Pro316, Thr347,Tyr89,Leu 348,Gln94,Asp153 ,Asp108,Pro107,Gl u155,Lys189 Tyr89,Ser91,Trp9 3,Arg228,His352, Glu182,Glu285,Tr p283,His193,Asn3 13,Ser315,Ser317, Pro316,Thr347,Le u348,Phe351,Trp9 3,Asp153,Asp108,

80

29. ZINC954864 11

-6.94

8.73 µM

4

Trp93, Gly192, His193, Thr347, Glu285, Arg228, Asn313, Leu348, Asp108, Ser191, Leu194, His193,

-5.8

3

His193,Ser315,S -168.903 8 er317,Ser191,Leu 194,Asn313,Leu3 48,His352,Phe35 1,Trp93

Glu155,Lys189 Trp93,Ser191,Gly 192,His193,Ser31 7,Thr347,Arg228, Glu285,Trp283,As n313,Ser315,His35 2,Leu348,Pro107, Asp108,Leu194

81

Supplementary Table 6: The occupancy of H-bonds formed between MtbICL and the predicted ligand molecule, during the last 20 ns simulation time period. Sr. No.

Amino acid residue Atom

1.

Ser91-Side-OG

MtbICL – ZINC130607 1 Atom O4

2.

Trp93-Main-N

O4

3.

Thr347-Side-OG1

4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

O3

% Amino acid Occupanc residue Atom y 59.24 Asn313-SideND2 His352-Side50.05 NE2 0.10 Tyr356-SideOH Leu194-Main-O Ser191-Main-O

MtbICL ZINC21110 81 Atom O6

% Amino acid Occupanc residue Atom y 0.30 Thr347-Side-OG1

O2 O2

1.20 2.00

O6 O5

0.10 0.10

Ser191-Side-OG Ser191-Side-OG

O8 O7

0.10 0.10

Ser191-Main-O

O6

0.20

Thr347-Side-OG1 Asp108-SideOD1 Leu194-Main-N Ser317-Side-OG Asn313-SideND2 Thr347-Side-OG1 Asn313-SideND2 Asn313-SideND2 Asp108-Side-CG Ser315-Side-OG Ser317-Side-OG Ser317-Side-OG

MtbICL ZINC2134917 Atom O6

% Occupancy

O7 N2

0.70 0.20

O5 O5

1.60 0.20

O6 O4

0.90 0.20

O4

8.19

O7 N2 O7 O6 O7

0.40 0.10 0.10 0.10 0.10

0.80

82

83

Supplementary Table 7: The occupancy of H-bonds formed between MtbICL and the reference ligand molecule, during the last 20 ns simulation time period.

Sr. No.

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.


MtbICL – Bromopy ruvate Atom GLN94-Side-NE2 O4 GLN94-Side-NE2 GLY192-Main-N GLY192-Main-N TYR89-Side-OH GLY192-Main-N GLN184-SideNE2 GLN94-Side-NE2 SER91-Side-OG TYR89-Side-OH ARG228-SideNH2 TYR89-Side-OH

% Occupa ncy


MtbICL Nitropropionat e Atom

% Occupancy

2.70%

ASP108-Main-N ASP108-Main-N ASP108-Main-N ASP108-Main-N SER110-Side-OG

OAH OAG OAD OAC OAG

2.60% 3.70% 0.30% 0.20% 0.10%

O2 O4 O2 O2 O3

3.20% 1.30% 0.70% 0.40% 3.00%

O2 O3 O4 O3

0.10% 0.10% 0.60% 0.20%

O3 O4

0.30% 0.40%

84

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