Effective Prediction of Best Inhibitor for Staphylococcus aureus through Molecular Docking 演講者 : 周慈敏 日期 :2016/5/30

Molecular Docking Predict the Best Inhibitor 2 Introduction Molecular docking is a simulation to mimic the interaction between ligand and receptor basing on "lock-key principle

Target + Ligand Complex 3 Molecular Docking Mechanism

Staphylococcus aureus Flavonoid 4

Structural Modifications 水溶性 分子較小 容易被人體吸收 5 Few drawback

6 Binding Mode of Protein-Ligand Complex

7 軟體 : AutoDock 方法 : Lamarckian Genetic Algorithm (LGA) 蛋白質來源 :1OH1 (Protein Data Bank, Ligand 繪圖軟體 :ChemDraw computational details

LGA 算法過程圖 8

9 Journal of Computational Chemistry, 19, (1998)

10 Result and Discussion

Ligand 1 (-6.95kcal/mol) Ligand 2 (-7.15kcal/mol) Ligand 3 (-7.27kcal/mol) Ligand 4 (-6.90kcal/mol) Ligand 5 (-7.10kcal/mol) Ligand 6 (-6.95kcal/mol) Ligand 7 (-6.82kcal/mol) Ligand 8 (-6.71kcal/mol) Ligand 9 (-7.28kcal/mol) Ligand 10 (-7.15kcal/mol) The Structure of Ligand

Ligand 11 (-6.98kcal/mol) Ligand 12 (-7.01kcal/mol ) Ligand 13 (-7.00kcal/mol) Ligand 14 (-6.95kcal/mol) 12 (-7.2kcal/mol) (-6.85kcal/mol)(-6.75kcal/mol) (-6.81kcal/mol) (-6.93kcal/mol)(-7.23kcal/mol)

(-7.46kcal/mol) (-7.47kcal/mol) 13 (-6.89kcal/mol) (-6.78kcal/mol) (-7.43kcal/mol)-6.85kcal/mol (-6.46kcal/mol) (-6.87kcal/mol)(-6.59kcal/mol) -6.6

Ligand 17 (-6.83kcal/mol) Ligand 18 (-6.95kcal/mol) Ligand 19 (-7.01kcal/mol) Ligand 20 (-6.93kcal/mol) Ligand 21 (-7.71kcal/mol) Ligand 22 (-6.99kcal/mol) Ligand 23 (-6.93kcal/mol) Ligand 24 (-7.50kcal/mol) Ligand 25 (-7.06kcal/mol) 14 The Structure of Ligand

LigandBinding Energy (kcal/mol)Hygrogen Bond Ligand ILE27 (1.753Å) GLY29 (2.173Å) Ligand ILE27 (1.697Å) GLY29 (1.866Å) 15 The Binding Energy and Their Hydrogen Bond Distance in Å

16 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41(2.033Å) ILE27 (1.789Å) Ligand GLY29 (1.881Å) ILE27 (1.750Å)

17 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41 (1.766Å) ILE27 (1.890Å) ILE27 (2.143Å) ILE26 (2.051Å) Ligand LEU41 (1.925Å) ILE27 (1.709Å)

18 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41 (1.985Å) ILE27 (1.829Å) Ligand LEU41 (2.025Å) ILE27 (1.767Å) ILE106 (2.003Å)

19 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41 (2.072Å) ILE27 (1.712Å)

Conformer of Ligand 17Conformer of Ligand 21 20

Interactions of ligand 17-protein complexes (ligand is resented in purple, hydrogen bond are resented in yellow) 21

Interactions of ligand 21-protein complexes 22

Ligand 26 (-6.93kcal/mol) Ligand 27 (-7.12kcal/mol) Ligand 28 (-6.91kcal/mol) Ligand 29 (-6.83kcal/mol ) Ligand 30 (-7.70kcal/mol) Ligand 31 (-7.01kcal/mol) Ligand 32 (-6.91kcal/mol) Ligand 33 (-7.51kcal/mol) Ligand 34 (-7.05kcal/mol) 23 The Structure of Ligand

24 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand GLY29 (1.881Å) ILE27 (1.750Å) Ligand LEU41 (1.797Å) ILE27 (1.708Å)

25 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41 (2.031Å) ILE27 (1.687Å) Ligand GLY29 (2.115Å) ILE27 (2.072Å) ILE27 (1.732Å)

26 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41 (1.684Å) ILE27 (1.828Å) ILE27 (2.095Å) ILE26 (1.993Å) Ligand LEU41 (1.995Å) ILE27 (1.696Å)

27 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41 (1.903Å) ILE27 (1.823Å) TYR31 (2.395Å) Ligand LEU41 (2.024Å) ILE27 (1.724Å) ILE106 (2.049Å) Ligand LEU41 (2.000Å) ILE27 (1.728Å)

Interactions of ligand 30-protein complexes 28

29 Ligand 21Ligand 30 LigandBinding Energy (kcal/mol)Hygrogen Bond Ligand LEU41(1.766Å) ILE27(2.143Å) TYR31(2.294) ILE26(2.051Å) Ligand LEU41(1.684Å) ILE27(1.828Å) ILE27(2.095Å) ILE26(1.993Å)

Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol 30 The Structure of Ligand

31 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41 (1.758Å) ILE27 (1.861Å) ILE27 (2.237Å) ILE26 (1.940Å) Ligand LEU41 (1.738Å) ILE27 (1816Å) ILE27 (2.119Å) ILE26 (2.021Å)

32 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41 (1.716Å) ILE27 (1.801Å) ILE27 (2.140Å) ILE26 (1.885Å) Ligand LEU41 (1.758Å) ILE27 (1.851Å) ILE27 (2.169Å) ILE26 (2.056Å)

33 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41(1.785Å) ILE27(1.795Å) ILE27(2.208Å) ILE26(1.823Å) Ligand LEU41(1.788Å) ILE27(1.800Å) ILE26(1.913Å)

34 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand ILE26(2.013Å) ILE27(2.093Å) ILE27(1.842Å) Ligand LEU41(1.804Å) ILE27(2.161Å) ILE26(1.980Å)

Interactions of ligand 36-protein complexes 35

Ligand 43 Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol 36 The Structure of Ligand

37 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand Ligand LEU41(1.788Å) ILE27(1.824Å) ILE27(2.126Å) ILE26(1.927Å)

38 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand ILE26(1.972Å) ILE27(1.974) ILE27(2.175Å) LEU41(1.792Å) Ligand LEU41(1.751Å) ILE27(1.790Å) ILE26(1.980Å)

39 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41(1.758Å) ILE27(2.184Å) ILE27(1.780Å) ILE26(1.790Å) Ligand LEU41(1.742Å) ILE27(1.801Å) ILE27(2.174Å) ILE26(1.804Å)

40 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand ILE26(1.961Å) ILE27(1.792) ILE27(2.150Å) LEU41(1.751Å) Ligand LEU41(1.738Å) ILE27(1.842Å) ILE26(2.008Å)

Interactions of ligand 44-protein complexes 41

Ligand 51 Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol Ligand kcal/mol 42 The Structure of Ligand

43 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand Ligand LEU41(1.775Å) ILE27(1.820Å) ILE27(2.143Å) ILE26(2.056Å)

44 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand ILEU41(1.767Å) ILE27(1.809) ILE27(2.230Å) LE26(1.825Å) Ligand LEU41(1.784Å) ILE27(1.785Å) ILE27(2.182Å) ILE26(1.807Å)

45 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41(1.838Å) ILE27(1.785Å) ILE26(1.896Å) Ligand LEU41(1.721Å) ILE27(1.877Å) ILE26(2.017Å)

46 Ligand Binding Energy (kcal/mol) Hygrogen Bond Ligand LEU41(1.753Å) ILE27(1.817) ILE27(2.187Å) ILE26(1.851Å) TRP31(2.239Å)

Interactions of ligand 52-protein complexes 47

Interactions of ligand 56-protein complexes 48

Interactions of ligand 57-protein complexes 49

50 較低 RMSD 值 MD simulation

Conclusion 51 以 AutoDock 來模擬蛋白質 - 配體對接部分， Ligand 52 ， Ligand 56 和 Ligand 57 擁有較低的結合能，分別是 : kcal/mol ， kcal/mol 以及 kcal/mol ，而在 MD simulation 中發現 Ligand 57 有比較小的 RMSD ，表示說 Ligand 57 有做為金黃色 葡萄球菌抑制劑的潛力。

Thanks for your kind attention 52