普恩蛋白疾病又名為傳染性海綿狀腦病，主要是正常型普恩蛋白結構上發生錯誤摺疊而轉變成致病型普恩蛋白，進而在腦部沉積成不可溶的纖維，造成神經細胞死亡。為了探討D178N和F198S人類突變型普恩蛋白結構特性和聚集機制的關係，本文利用分子動力學模擬在不同溫度與酸鹼值條件下，將原本是單體的普恩蛋白(I-178、I-198)和已形成雙體普恩蛋白拆解後的單體(II-178、II-198)比較之下，期望藉由結構的動態行為找出影響普恩蛋白聚集前的中間態結構。結果顯示，酸性pH值條件下容易誘使β摺板(β-sheet)延展，Helix 2易受到環境擾動而展開，最後從蛋白質-蛋白質交互作用的平均能量推論，II-178和II-198的殘基片段165-170以及186-194可能是引發聚集的關鍵序列。

Prion disease, also called transmissible spongiform encephalopathy (TSE), is the conformational transition of the physiological cellular form (PrPC) to a pathological scrapie form (PrPSc), resulting in misfolding to insoluble fibrillar aggregates deposited in our cerebellum. To investigate the implication of structural characteristics and aggregation mechanism of human prion protein mutant D178N and F198S, we performed molecular dynamics simulations under various temperatures and pH values on two types of models : original monomeric form referred to first type (I-178, I-198) and the monomer from natural dimeric form referred to second type (II-178, II-198). Furthermore, it is expected that the structural dynamically behaviours of prion protein intermediates could be identified before aggregating to oligomers even to fibrils. The significant results have indicated that all of monomeric forms sensitively triggered the elongation of β-sheet transition under low pH condition, noteworthily, the C-termini of helix 2 domain were destabilized via environmental perturbations. Eventually, we made a conclusion through protein-protein interaction energy distributions that the segments 165-170 and 186-194 for second type of prion protein are probably the crucial event linked to aggregation steps.

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