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研究生:許耀華
研究生(外文):Yao-Hua Hsu
論文名稱:人類免疫缺陷病毒之蛋白水解酶抑制劑其活性、分子接合能量與分子凸狀殼關係之研究
論文名稱(外文):A study of the relationship between activity, docking energy and convex hull descriptors of HIV protease inhibitors
指導教授:林志侯
指導教授(外文):Thy-Hou Lin
學位類別:碩士
校院名稱:國立清華大學
系所名稱:生物技術研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:78
中文關鍵詞:接合描述器羅吉司回歸定量結構-活性關係
外文關鍵詞:dockdescriptorlogistic regressionQuantitative structure-activity relationship
相關次數:
  • 被引用被引用:1
  • 點閱點閱:156
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
隨著計算機科學的快速進展,結合電腦圖形、藥學和結構生物學的工具來加速藥物的開發已漸漸成為藥物設計中的重要課題,而其中定量結構-活性關係(Quantitative structure-activity relationship)模型的建立與分子接合模擬(Molecular docking)是許多藥廠非常感興趣的領域。本論文即針對338個有活性的愛滋病病毒蛋白水解酶抑制劑(HIV protease inhibitor)進行了一系列的分子凸狀殼(Convex hull)特性計算與分子接合(docking)模擬,目的在找出分子凸狀殼、接合能量與活性之間的關係以作為往後改良分子描述器之參考。透過傳統迴歸分析與羅吉斯迴歸(Logistic regression)的方法,我們發現分子凸狀殼雖無法直接建立與活性的線性關係,但其與活性間卻存有一個群集(Clustering)的關係。此外我們也發現若對活性與分子模擬接合之能量進行相關分析,其中並無顯著的相關性。這顯示了若欲建立分子接合能量與活性間的相關模型,我們勢必要建立一個更精確的評分函數(Scoring function)與較為完整的結構搜尋方式。
With the rapid progression in computational science, methods that integrate computer graphics, pharmacology and structural biology to accelerate drug development have become an important subject in drug design. Among these methods, building of quantitative structure-activity relationship(QSAR)model and molecular docking simulation are areas that drug companies especially interested in. In this thesis, the relation- ship between molecular convex hull property, docking energy and activity has been studied by using 338 HIV protease inhibitors as material. With the use of conventional regression and Logistic Regression, we have found that although the linear regression model can not be built, it does exist a clustering relationship between our convex hull descriptor and activity. In addition, there is not an obvious relationship between docking energy and activity. In order to build a model between activity and docking energy, a more precise scoring function and structure -searching algorithm should be developed.
中文摘要 -------------------------------------------------------------------------- 1
英文摘要 -------------------------------------------------------------------------- 2
第一章 序論 -------------------------------------------------------------- 3
第一節 研究動機 -------------------------------------------------------- 3
第二節 研究目的 -------------------------------------------------------- 4
第二章 文獻探討 -------------------------------------------------------- 5
第一節 HIV-1與HIV-1 PR之特性描述 -------------------------------- 5
第二節 凸狀殼理論 -------------------------------------------------------- 10
第三節 分子接合 -------------------------------------------------------- 11
第三章 材料與方法 -------------------------------------------------- 17
第一節 PI分子結構之建立 -------------------------------------------- 17
第二節 凸狀殼描述器計算 -------------------------------------------- 18
第三節 分子接合模擬流程與參數設定 -------------------------------- 19
第四章 結果 -------------------------------------------------------------- 21
第一節 分子凸狀殼性質與活性之線性關係模型建立 -------------- 21
第二節 分子凸狀殼性質與活性之羅吉斯迴歸模型建立 ----------- 23
第三節 接合能量與活性之相關性分析 -------------------------------- 24
第五章 討論 -------------------------------------------------------------- 26
第一節 分子凸狀殼描述器之模型討論 -------------------------------- 26
第二節 分子接合模擬結果之討論 -------------------------------------- 27
第六章 參考資料 -------------------------------------------------------- 56
附錄 338個HIV PI之分子結構與活性表 -------------- 62
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