CADD Project Report 學號: 姓名:

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

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

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

Target Protein and Ligand 4dfr MTX

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

NMDA receptors are the Glutamate receptor ionotropic

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

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)

Disulfide bonds

Ligand present 2 GLU C5 H9 N O4

Mechanism of Drug Actions 3 Nature vol 438|10 Nov. 2005|doi:10.1038/nature04089

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

Molecular Docking Using iGEMDOCK 4 Standard Docking

Rank 5

SiMMap 6

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

Similar Compound Search 8

9 30 Compounds 1 895124 11 1631039 6 1730673 2 901627 12 1631040 7 1747050 3 901628 13 1672628 8 1757297 4 901823 14 1672629 9 2003955 5 1482113 15 1672630 10 2035153 1530091 1672631 3869949 1532877 1683185 3870045 1571334 1694469 6360498 1631037 1694472 6360532 1631038 1700280 13525354

Molecular Docking Using iGEMDOCK 10 Accurate Docking

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

Table of Docking Energy 1 -102.67 11 -100.33 6 -89.2 2 -114.16 12 -106.44 7 -109.05 3 -105.31 13 -105.66 8 -99.29 4 -99.02 14 -113.44 9 -109.53 5 -109 15 -105.74 10 -91.11 -96.6 -104.92 -92.35 -97.21 -109.22 -98.28 -88.91 -124.01 -114.92 -109.3 -116.02 -106.16 -107.9 -103.64 -109.97

Figure of Docking Energy 1 3 5 2 4 Energy Compound

Interaction Profile

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

Top1 12  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC20113196

Top2  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC20113196

Top3  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC20113196

Top4  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC20113196

Top5  4-[[3-hydroxy-2-methyl-5-(phosphonooxymethyl)-4-pyridyl]methyleneamino]butanoic K56 R135 G186 G185 F55 E1 E2 V1 ZINC20113196

Conclusion 13