- 學位論文
人類普利昂蛋白於不同溫度下之分子動力學模擬
Molecular Dynamics Simulations of Human Prion Protein under the Different Temperatures
摘要
傳染性海綿狀腦病(Transmissible spongiform encephalopathies, TSEs)是由腦部神經細胞漸進性的死亡引起。當取出傳染性海綿狀腦病患者的腦組織檢查時，可以看到腦部組織呈現海綿狀的外觀。一般相信普利昂蛋白與傳染性海綿狀腦病的發生有關。普利昂蛋白有兩種構形，即自然的構形和變性後的構形。傳染性海綿狀腦病的普利昂蛋白會誘導正常的普利昂蛋白摺疊成為致病的形態。錯誤的摺疊聚集成堆會干擾細胞的功能及引起細胞的死亡。本研究利用分子動力學模擬的方式，探討人類普利昂蛋白於不同溫度下的情況和變化。由於蛋白質的功能會受到蛋白質的折疊方式所影響，而折疊方式也會受到熱能的影響。我們以CHARMM來進行分子動力學模擬，計算人類普利昂蛋白於不同溫度下的分子振動情形。我們從RCSB的蛋白質資料庫PDB（Protein Data Bank）取得人類普利昂蛋白PDB ID為1i4m的結構資料，以GB模組的假想位勢模擬水環境，模擬人類普利昂蛋白於室溫(300K)、人體內溫度(310K)等溫度之下的動態行為。模擬每步數的時間為2*10^(−15)秒，總步數為1.5*10^6步，總時間為3*10^(−9)秒(3ns)。我們計算原子的振動(Root-Mean-Square Deviation, RMSD)、殘基的位移(Root-Mean-Square Fluctuation, RMSF)、旋轉半徑(Radius of Gyration, RGYR)等，發現於不同溫度之下，人類普利昂蛋白會有不同的構形。
並列摘要
The symptoms of transmissible spongiform encephalopathies(TSEs) are caused by the progressive death of the brain's nerve cells. When brain tissue collected from a TSEs patient is examined, the spongy appearance of the brain tissue can be found. The prion that is believed to cause TSEs exhibits at least two conformations, the native state and the other conformational state. The TSEs prion promotes refolding of native proteins into the diseased state. Mass of misfolded proteins disrupts cell function and causes cell death. In this study, we performed molecular dynamics simulations by using CHARMM. Calculation of human prion protein in different temperatures associated with the molecular vibration. We obtained human prion protein PDB ID=1i4m structural information from the RCSB protein data bank (PDB). Simulation of water environment use GB imaginary potential. Simulations of human prion protein dynamic behavior were carried out at room temperature (300K) and human body temperature (310K) etc. Each simulation time step was set to 2*10^(−15) seconds. Total steps set to 1.5*10^6 steps. The total simulation time is 3*10^(−9) seconds (3ns). We calculated Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF) and Radius of Gyration (RGYR). It demonstrated that the conformations of human prion protein change under different temperatures.