CADD Project Report 學號: 姓名:.

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1 CADD Project Report 學號: 姓名:

2 胡庭斳 王靖崴 胡 媗 林羿萱 陳品賢 許富善 李炘杰 李宗禧 張旭欣 陳 新 林靖雅 謝亦嘉 唐 榕 蔡政融 葉卓森 余紹瑋 林昭翰
Name Protein PDBID Ligand 胡庭斳 王靖崴 胡　媗 林羿萱 陳品賢 許富善 李炘杰 李宗禧 張旭欣 陳　新 林靖雅 謝亦嘉 唐　榕 蔡政融 葉卓森 余紹瑋 林昭翰

3 Protein PDBID Ligand 1 1hri S57 11 1yee PNB 2 1vrh SD8 12 1epo 2Z3 3 1qbu 846 13 1aj7 NPE 4 1mnc PLH 14 1mts BX3 5 1ctr TFP 15 1b9v RA2 6 1dwc MIT 16 1qbr XV6 7 1f3d TPM 17 1aoe GW3 8 1kno PNP 18 1ejn AGB 9 1elc 0Z3 19 1ive ST3 10 1byg STU 20 2ctc HFA

4 Ligand in target Protein
1 2 Test Set : 310 Ligands ZINC Database Target Protein : 4dfr Ligand in target Protein 4 8 iGemDock (Standard) Similar Compound Search (tanimoto 40) 5 9 310 Docked Pose Top 15 Compounds 15 compounds 6 10 SiMMap iGemDock (Accurate) 7 Anchors Top 5 Compounds 12 11 PDB Docking Pocket Analysis(PyMol) Post-screening Analysis 3 13 Mechanism of Drug Actions Conclusion

5 Target Protein and Ligand
4dfr MTX

6 Introduction of Target Protein
1 What is this protein? (from paper) How many chains? Please show the secondary structure. Are there any disulfide bonds? 4dfr

7 NMDA receptors are the Glutamate receptor ionotropic

8 指令： color by chain 兩種顏色代表含有兩條chain A chain：green B chain：blue

9 針對A、B chain 紅色代表 a-helix (共含有17條) 黃色代表 b-sheet(共含有29條) 綠色代表 loop (共含有42條)

10 Disulfide bonds

11 Ligand present 2 GLU C5 H9 N O4

12 Mechanism of Drug Actions
3 Nature vol 438|10 Nov. 2005|doi: /nature04089

13 Nature vol 438|10 Nov. 2005|doi:10.1038/nature04089

14 Molecular Docking Using iGEMDOCK
4 Standard Docking

15 Rank 5

16 SiMMap 6

17 SiMMap Anchors 7 G186 G185 V1 E1 PLP R135 F55 MLI E2 K56

18 Similar Compound Search
8

19 9 30 Compounds 1 895124 11 6 2 901627 12 7 3 901628 13 8 4 901823 14 9 5 15 10

20 Molecular Docking Using iGEMDOCK
10 Accurate Docking

21 Post-screening Analysis
11 Table of Docking Energy Figure of Docking Energy Interaction Profile Interaction Analysis

22 Table of Docking Energy
1 11 6 -89.2 2 12 7 3 13 8 -99.29 4 -99.02 14 9 5 -109 15 10 -91.11 -96.6 -92.35 -97.21 -98.28 -88.91 -109.3 -107.9

23 Figure of Docking Energy
Energy Compound

24 Interaction Profile

25 Interaction Analysis 紅色部分是指靠電子吸引的鍵結 綠色部分是指靠氫鍵的鍵結 灰色部分是指靠凡得瓦力的鍵結 18 34
19 49 28 2 紅色部分是指靠電子吸引的鍵結 綠色部分是指靠氫鍵的鍵結 灰色部分是指靠凡得瓦力的鍵結

26 Top1 12  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC

27 Top2  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC

28 Top3  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC

29 Top4  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC

30 Top5  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC

31 Conclusion 13