請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/16914
標題: Conformational Analysis of 2,2'-Bis-(N-alkylcarbamyloxy methyl) biphenyls by Quantum Chemistry and Molecular Dockings of these Inhibitors into X-ray Crystal Structure of Lipase
聯苯胺基甲酸類抑制劑用量子化學構型分析和其與脂肪酵素X-射線結晶之分子對接
作者: 黃詩婷
Huang, Shih-Ting
關鍵字: Inhibitor
抑制劑
Lipase
Molecular Docking
脂肪酵素
分子對接
出版社: 化學系所
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[ J ] , 1995, 9(2): 113 37. Wang J., Kollman P. A., Kuntz I. D. Prot. Struct. Funct. Genet. [ J ] , 1 999, 36 : 1 38. Mangoni M., Roccatano D., Nola A. D. Prot. Struct. Funct . Genet. [ J ] , 1999 , 35(2): 153 39. Goodsel l D. S., Olson A. J. Prot . Struct. Funct. Genet. [ J ] , 1990, 8(3): 195 40. Morris M. G., Goodesll S. D., Huey Ruth, et al. Distributed automated docking of flexible ligands to proteins: Parallel applications of Autodock2.4. J Comput-Aided Mol Design, 1996(10): 293 41. Stockwel l B. R., Nature [ J ] , 2004, 432: 846 42. Gialih L., Ching-Ing H., Ju-Yueh C., Hou-Jen T., Conformational Analysis of Biphenyl Derivatives. I. A Novel Steric Constant from the Internal Rotation Rate of 2,2'-Bis-(N-Substituted Carbamoylmethyl) Biphenyl by Means of Dynamic NMR. Journal of the Chinese Chemical Society 47, 449-454(2000). 43. Marco N., Dietmar A. L., Klaus L., Karl-Erich J., Bauke W. D., Crystal Structure of Pseudomonas aeruginosa Lipase in the Open Conformation. 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摘要: 聯苯胺基甲酸類的八個抑制劑在脂肪酵素中皆可產生抑制效果,利用Autodock軟體模擬將聯苯胺基甲酸類抑制劑放入脂肪酵素中的活性中心附近,也就是原三酸甘油酯的反應位置,模擬完後與活性位置比較篩選適合的構型。 將得到的構型與脂肪酵素的活性位置、產生的氫鍵、相對的KI值、Binding Energy加以比較,得到抑制效果最佳的抑制劑,並比較此類抑制劑是否有trans- carbamate或cis-carbamate的抑制效果較好。 並利用Gaussian 09 推測抑制劑進入脂肪酵素時所需的旋轉能障及各抑制劑最低能量的構型。經Gaussian 09的模擬計算後,發現是trans- carbamate較cis-carbamate穩定,而由trans- carbamate轉到transition state最高也只有41kJ/mol,相較於轉動中軸Biphenyl bond,轉動carbamate的能量並不高,轉動中軸Biphenyl bond的能量約為68~100 kJ/mol,轉動中軸的能障較為重要,因為當抑制劑要進入脂肪酵素時有可能會因為中間的苯環互相垂直而卡住洞口,阻礙抑制劑的進入。
Molecular Docking of 2,2'-bis-(N-alkylcarbamyloxy methyl) biphenyls into X-ray crystal structure of pseudomonas aeruginosa lipase confirmed the experimental results from the literature. From quantum chemistry calculation, rotation energy for the biphenyl bond and trans- to cis-carbamate rotamer of these Inhibitors dynamic NMR results from the literature.
URI: http://hdl.handle.net/11455/16914
其他識別: U0005-2706201216551300
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2706201216551300
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