- 學位論文
蛋白質熱穩定性之分子動力學模擬
Molecular Dynamics Simulations of the Thermal Stability of Proteins
摘要
本研究利用分子動力學模擬(Molecular dynamics simulations, MD simulations)研究蛋白質之熱穩定性，由於蛋白質的功能會受到蛋白 質的構形影響，而構形會受到熱能的破壞。而分子動力學模擬是使用 CHARMM 進行模擬。以CHARMM 模擬後，計算於水溶液中蛋白質 在不同溫度下的分子振動情形。我們從蛋白質資料庫(Protein Data Bank, PDB)選擇並取得兩個蛋白質的結構資料，其中之一為嗜高溫 蛋白質1CAA (Tm = 110℃)；而另一個是嗜中溫蛋白質1IRO (Tm = 35.5℃)。它們是屬於Rubredoxin 家族的同源單體蛋白質。建立一個 水溶液模擬環境(water-box)，並將兩蛋白質置入水溶液環境中，以分 子動力學模擬研究它們的動態行為。模擬的溫度分別設定為絕對溫 度300 K 與373 K。模擬結果顯示，蛋白質的分子振動(RMSD)與溫 度有關聯性。另一方面，以B-factor 代表真實狀態，而以RMSF 代表 電腦模擬狀態；由模擬的結果發現兩個蛋白質的RMSF 與B-factor 確 實有相關性，其相關係數分別為0.79 與0.96。對嗜高溫蛋白質與嗜 中溫蛋白質於不同溫度中的分子振動情形，以RMSD、RGYR、RMSF 以及B-factor 四項數值比較後，發現嗜高溫蛋白質的分子振動都比嗜 中溫蛋白質的分子振動小，因此證實可以由蛋白質的分子振動來推測 蛋白質的熱穩定性。
並列摘要
In this study, the thermostability of proteins was studied using the molecular dynamics (MD) simulations, since the protein functions were controlled by protein thermal stability. The MD simulations were carried out by using CHARMM. We selected two proteins, 1IRO and 1CAA, from the Protein Data Bank (PDB). One protein (1CAA) is hyperthermophilic (Tm = 110℃) and the other (1IRO) is its mesophilic counterpart (Tm = 35.5℃). They are homologous proteins and are belonged to Rubredoxin family. A simulated water-box was created and a protein was put in it to study a dynamic behavior. The temperatures of simulations were 300K and 373K. The results of simulations display the root-mean-square deviations (RMSDs) for the proteins are dependent on temperatures. Furthermore, the root-mean-square fluctuations (RMSFs) are correlated with the B-factors of the two proteins. The correlated parameters are 0.790182 for 1IRO and 0.963055 for 1CAA. The molecular vibration of hyperthermophilic and mesophilic proteins could be observed in different temperatures. The molecular vibration of mesophilic protein is greater than hyperthermophilic one, by comparing RMSD, RGYR, RMSF and B-factor values. Therefore, the thermostability of proteins may predict by observing their molecular vibrations.