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| 研究生： |
李育銘 Yu-Ming Lee |
|---|---|
| 論文名稱： |
心臟毒蛋白及其一月生月太片段折疊之計算研究 Examination of refolding of the cardiotoxin III from Taiwan cobra venom and its peptide using molecular dynamics simulationmn |
| 指導教授： |
孫英傑
Sun, Ying-Chieh |
| 學位類別： |
碩士 Master |
| 系所名稱： |
化學系 Department of Chemistry |
| 論文出版年： | 2002 |
| 畢業學年度： | 90 |
| 語文別： | 中文 |
| 論文頁數： | 120 |
| 中文關鍵詞： | 分子動力學模擬 、蛋白質折疊 、蛋白質再折疊 、心臟毒蛋白三 、內涵水合模型 |
| 英文關鍵詞： | molecular dynamics simulation, protein folding, protein refolding, CTX III, implicit solvation model |
| 論文種類： | 學術論文 |
| 相關次數： | 點閱：184 下載：0 |
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蛋白質折疊是生命科學領域中一個基本且重要的問題。台灣眼鏡蛇毒蛋白分子三（CTX III）是一個全部由β-摺板結構組成的小蛋白質，共有60個胺基酸，五個β-摺板。本論文對這個蛋白質分子做了16條的再折疊的分子模擬動力學模擬軌跡，並且試著由這些模擬軌跡來探討這個CTX III蛋白質再折疊的路徑。模擬結果發現，在16條模擬軌跡中，有5條成功地折成NMR類似結構，在大部分的模擬軌跡中，β345都會先形成，β12由於屬於擾動性較大的結構，較不易形成。經由構形簇分析得到的過渡態、中間態結構中氫氫對的距離與實驗上由NOE訊號推得之CTX III部份展開結構有良好的一致性；此外，NMR結構的氫鍵中氫的保護係數與再折疊軌跡中的氫鍵的形成比率在定性上亦有不錯的相關度；在此我們亦描述了一條成功軌跡的再折疊路徑。根據模擬結果，本論文建議，雙硫鍵對折疊核心結構具有重要的穩定性，折疊核心之疏水效應可能具有引導β12之氫鍵形成的效果。另外，我們亦將CTX III之β34股單獨切下做β-髮夾的再折疊模擬並探討其再折疊路徑。歸納10條模擬軌跡發現，同一種序列之β-髮夾可能循兩種不同的折疊路徑折疊，這兩種再折疊路徑分別為上拉鍊模型以及下拉鍊模型。模擬結果指出，前者是因為第一對位於轉彎結構附近形成的氫鍵所引導；後者是位於尾部的幾對氫鍵一起形成所致，顯示這些氫鍵形成的合作效應。我們報告討論這兩種折疊路徑的特徵以及氫鍵形成順序的異同。
Protein folding is one of the most fundamental and important problems in life science. Taiwan Cobra Cardiotoxin III（CTX III）is a small all-β-sheet protein of 60 amino acids and 5 β-sheets. Molecular dynamics simulations of CTX III were carried out to examine the refolding pathway(s) of this protein. In our simulations, 5 of 16 trajectories successfully refolded into NMR-like structure. Experimentally, it was observed thatβ-sheet of strand III, IV and V are formed earlier than β-sheet of strand I and II. The simulations gave the same result. From the refolding trajectories, transition states and intermediate states were identified using a conformational-cluster analysis. The calculated transition state structure showed good consistency with the experimental partially unfolded structure based on NOE data. It also noted that some calculated H-bond formation percentage correlate qualitatively well with experimental H-bond donor protection factors. The result of a refolding trajectory, which folded close to NMR structure, suggests that the disulfide bonds play an important role in CTX III folding, and the hydrophobic effect in head region may guide the hydrogen bond formation of β-strand I and II in CTX III. In addition to CTX III simulations, we cut residue 20-39 from CTX III and simulate 10 trajectories for this peptide to examine if this peptide form a β-hairpin. The simulations show that the H-bonds between two strands can form either in zip-up or zip-down direction. Formation of H-bonds showed cooperative effect. We report and discuss the physical basis of these simulated results.
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