貝他糊蛋白(Aβ)聚合物被認為與阿茲海默式症有很大的關連性。根據實驗發現，Aβ21-30此序列折疊成核過程中會產生Aβ的病理學聚合作用。在本文中，利用分子動力學探討Aβ21-30(wild-type)與其同源物E22Q (Dutch), E22K (Italian), E22G (Arctic), and D23N (Iowa)的初始折疊過程與Val24-Lys28迴圈的穩定性，此迴圈被認為是影響Aβ形成病理學結構的主要原因。這些突變物對於背骨結構的影響性也是一個非常有趣的研究。在本文模擬結果中發現，wild-type和D23N二個模型中會形成穩定的背骨結構。另一方面，替換胺基酸殘基22(Glu)會使得疏水性作用力與鹽橋無法產生，因缺乏此些作用力的產生進而破壞Val24-Lys28迴圈的穩定性；然而在wild-type和D23N結果中，因疏水性作用力和殘基24和27所產生的氫鍵導致背骨結構穩定。此結果顯現，替換胺基酸殘基23(Asp)會增加Val24-Lys28迴圈的穩定性。

The assembly of amyloid β-protein (Aβ) into oligomers is linked to Alzheimer’s disease. Experimental evidences have shown that Aβ21-30, a decapeptide segment of Aβ, nucleates the folding process that results in the pathologic oligomerization of Aβ. In this study, molecular dynamics (MD) techniques were employed to probe the initial stages of folding of the wild type (WT) Aβ21-30 decapeptide and the homologous decapeptides of the E22Q (Dutch), E22K (Italian), E22G (Arctic), and D23N (Iowa) mutants in order to investigate the stabilizing effects of the Val-24—Lys-28 loop, which is postulated as a critical factor effecting Aβ to fold into pathological structures. The stabilizing effects of these mutations on the backbone structure of Aβ21-30 decapeptide are also interested. Numeric results of the present MD simulations show that, with the use of a common simulation time span, only WT and D23N model performed stable backbone conformations in the sense that steady root mean square deviation of the backbone Cα from the initial structure can be achieved in both models. The amino acid substitutions at residues 22 destabilize the Val-24—Lys-28 loop conformation in WT Aβ21-30 because of the lack of the hydrophobic interaction and salt bridge. Moreover, the present results reveal that the stable backbone conformations in WT and D23N Aβ21-30 are mainly attributed to the hydrophobic interaction between the side chains of Val-24 and Lys-28 and the hydrogen bonds Val-24(N)-Asn-27(O) and Asn-27(N)-Val-24(O). The results show that the amino acid substitution at Asp-23 could stabilize the Val-24—Lys-28 loop conformation.

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