Molecular dynamics simulations of spontaneous fibril formation by random-coil peptides
Molecular dynamics simulations of spontaneous fibril formation by random-coil peptides
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DOI：
10.1073/pnas.0407273101
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发表时间：
2004-11-16
影响因子：
11.1
通讯作者：
Hall, CK
中科院分区：
文献类型：
--
作者：
Nguyen, HD;Hall, CK
正常可溶性蛋白质组装成淀粉样纤维是许多人类疾病的原因或相关症状，包括阿尔茨海默病和朊病毒疾病。我们报告分子水平的模拟自发原纤维的形成。含有12-96个模型聚丙氨酸肽的系统在高于临界温度的温度下形成原纤维，该临界温度随肽浓度降低并超过肽的折叠温度，这与实验发现一致。小的无定形聚集体的形成先于有序的核形成和随后的快速原纤维生长，通过横向添加β-折叠和在原纤维末端添加单体肽。原纤维的结构与实验观察到的相似。
Assembly of normally soluble proteins into amyloid fibrils is a cause or associated symptom of numerous human disorders, including Alzheimer's and the prion diseases. We report molecular-level simulation of spontaneous fibril formation. Systems containing 12-96 model polyalanine peptides form fibrils at temperatures greater than a critical temperature that decreases with peptide concentration and exceeds the peptide's folding temperature, consistent with experimental findings. Formation of small amorphous aggregates precedes ordered nucleus formation and subsequent rapid fibril growth through addition of beta-sheets laterally and monomeric peptides at fibril ends. The fibril's structure is similar to that observed experimentally.