CADD Project Report 學號: 姓名:

# Name Protein PDBID Ligand 1 柯宏欣 黃翎瑄 1-10 2 姚秉宏 劉守軒 11-20 3 張景富 曾賀德 21-30 4 徐　綾 蕭廷怡 31-40 5 崔雁茹 戴若雲 41-50 # Name Protein PDBID Ligand 6 鍾妮津 許芯緁 51-60 7 張哲綱 柯廷揚 61-70 8 許潔馨 鄭宇倫 71-80 9 王靖涵 柯紹文 81-90 10 姚佳伶 周昱吟 91-100

http://gemdock.life.nctu.edu.tw/dock/download.php Target Protein Compounds 990

Protein: cav1aaq_PSI.pdb Ligand : pdb1aaq_PSI.mol + 1 2 2 Test Set : 990 Ligands ZINC Database Protein: cav1aaq_PSI.pdb Ligand : pdb1aaq_PSI.mol + 4 5 9 iGemDock (Standard) Rank: 3/991 Similar Compound Search (Tanimoto-60) 8 10 991 Docked Pose Top 15 Compounds 10 compounds 6 11 SiMMap iGemDock (Accurate) 7 Anchors Top 5 Compounds 13 12 PDB Docking Pocket Analysis(PyMol) Post-screening Analysis 3 14 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

Top15 Compounds from 990 set 8 # Ligand ID Energy 1 MFCD00000058 11 2 12 3 13 4 14 5 15 6 7 8 9 10

Similar Compound Search 9 Tanimoto-60

10 Compounds from similarity search 2 # Ligand ID 1 ZINC895124 2 ZINC901627 3 ZINC901628 4 ZINC901823 5 ZINC1482113 6 ZINC1530091 7 ZINC1532877 8 ZINC1571334 9 ZINC1631037 10 ZINC1631038 3 4

5 6 7 8 9 10

Molecular Docking Using iGEMDOCK 11 Accurate Docking

Post-screening Analysis 12 Table of Docking Energy Figure of Docking Energy Interaction Profile Interaction Analysis

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

Figure of Docking Energy 1 3 5 2 4 Energy Compound

Interaction Profile of Top5

Interaction Analysis of Top5 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 13  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 14