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研究生: 黃皇凱
Huang, Huang-Kai
論文名稱: 以分子動力學研究tRNA(Lys3)與HIV引子結合區之交互作用
Study the interactions between tRNA(Lys3) and HIV primer binding site by molecular dynamic.
指導教授: 黃吉川
Hwang, Chi-Chuan
學位類別: 碩士
Master
系所名稱: 工學院 - 工程科學系
Department of Engineering Science
論文出版年: 2010
畢業學年度: 98
語文別: 中文
論文頁數: 72
中文關鍵詞: HIV-1tRNALys3反轉錄分子動力學引子結合區引子激活信號
外文關鍵詞: HIV-1, tRNALys3, Reverse transcription, Molecular Dynamic Simulation, PBS, PAS
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  • HIV-1病毒是一種反轉錄病毒,其病毒RNA上的引子結合區(PBS)會與tRNALys3之反引子結合區(anti-PBS)進行互補交互作用,產生18組鹼基對,並開啟一連串反轉錄步驟。本文乃以分子動力學研究觀察此一作用區域之動態行為、分子穩定性及結構特徵,結果顯示在胺基酸接受端(3’-CCA)與反密碼環為整個tRNALys3中較不穩定的部分,而在其他種類之tRNA亦有類似之結果。此外,本文並比較不同長度之PBS與tRNALys3交互作用後的差異性,藉此了解TΨC臂下半部的PAS對反轉錄作用所產生之影響。由本文的研究結果發現,發現隨著anti-PAS上被占住的氫鍵數的增加,活性則隨著降低,反之則增加。

    Virus HIV-1 is one of retrovirus, which RNA primer binding of virus (PBS) will complementary interact with anti-primer binding site(anti-PBS) in tRNALys3. There are 18 base pairs and a series of reverse transcription steps will be produced during the complementary interaction of PBS and anti-PBS. In this study, molecular dynamics is utilized to observe the dynamic behavior , molecular stability and the structure of tRNALys3. The results show that in the amino acid accept stem (3’-CCA) and the anti-codon loop are the unstable part in tRNALys3. The similar results are found in the other type of tRNA. Additionally in order to realize the efficiency of reverse transcription of primer activation signal (PAS), the difference between the interaction of primer binding site (PBS) and tRNALys3 with different lengths is also compared in this study. The experimental results, In this study, the results shows that the activity will decrease with the increasing of the hydrogen bonds in anti-PAS.

    摘要 i Abstract ii 致謝 iii 目錄 iv 表目錄 v 圖目錄 vii 第一章 緒論 1 1-1研究背景 1 1-1-1 HIV病毒背景介紹 1 1-1-2 HIV生命週期和反轉錄機制介紹 3 1-2文獻回顧 7 1-3研究動機 13 1-4 本文組織架構 14 第二章 分子模型的建構與模擬方法 16 2-1 研究相關之網路資料庫 16 2-1-1 RCSB網路資料庫 16 2-1-2 PRODRG 2.5 Server -線上格式轉換 18 2-2 物理模型建構 20 2-2-1 初始結構的取得 20 2-2-2 修飾核苷酸的建置 21 2-3 分子動力學理論 30 2-3-1 勢能函數 30 2-3-2 溫度修正方法 32 2-3-3 加速運算方法 33 2-4 分子動力學模擬軟體 39 2-5 模擬步驟 42 第三章 結果與討論 45 3-1 轉移核醣核酸(tRNA) 整體構形穩定度分析 45 3-1-3 能量分析 45 3-1-1 均方根偏差( RMSD)分析 47 3-1-2 均方根波動( RMSF)分析 50 3-2 Primer Binding Site 長度對引子tRNALys3與 HIV病毒RNA複合體形成之影響 54 3-3 探討病毒反轉錄活性與引子激活信號(Primer Activation Signal, PAS) 之關係 57 第四章 結論 59 第五章 未來展望 60 參考文獻 62 附錄 A 模擬參數設定 66 能量極小化 - 最陡梯度法 (SD) 66 能量極小化 - 共軛梯度法 (CG) 67 MD模擬前預處理 68 MD模擬 70 作者自述 72

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