Nguyen Hung D, Hall Carol K
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695-7905, USA.
Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16180-5. doi: 10.1073/pnas.0407273101. Epub 2004 Nov 8.
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.
正常可溶的蛋白质组装成淀粉样纤维是许多人类疾病的病因或相关症状，包括阿尔茨海默病和朊病毒病。我们报告了自发纤维形成的分子水平模拟。含有12 - 96个模型聚丙氨酸肽的系统在高于临界温度时形成纤维，该临界温度随肽浓度降低且超过肽的折叠温度，这与实验结果一致。小的无定形聚集体的形成先于有序核的形成，随后通过横向添加β - 折叠和在纤维末端添加单体肽实现快速的纤维生长。纤维的结构与实验观察到的结构相似。
