Ilie Ioana M, Caflisch Amedeo
Department of Biochemistry, University of Zürich, Zürich CH-8057, Switzerland.
Chem Rev. 2019 Jun 26;119(12):6956-6993. doi: 10.1021/acs.chemrev.8b00731. Epub 2019 Apr 11.
Amyloids, fibrillar assembly of (poly)peptide chains, are associated with neurodegenerative illnesses such as Alzheimer's and Parkinson's diseases, for which there are no cures. The molecular mechanisms of the formation of toxic species are still elusive. Some peptides and proteins can form functional amyloid-like aggregates mainly in bacteria and fungi but also in humans. Little is known on the differences in self-assembly mechanisms of functional and pathogenic (poly)peptides. We review atomistic and coarse-grained simulation studies of amyloid peptides in their monomeric, oligomeric, and fibrillar states. Particular emphasis is given to the challenges one faces to characterize at atomic level of detail the conformational space of disordered (poly)peptides and their aggregation. We discuss the difficulties in comparing simulation results and experimental data, and we propose new simulation studies to shed light on the aggregation processes associated with amyloid diseases.
淀粉样蛋白是（多）肽链的纤维状聚集体，与阿尔茨海默病和帕金森病等神经退行性疾病相关，目前尚无治愈方法。有毒物种形成的分子机制仍然难以捉摸。一些肽和蛋白质主要在细菌和真菌中，也在人类中形成功能性淀粉样蛋白样聚集体。关于功能性和致病性（多）肽自组装机制的差异知之甚少。我们综述了淀粉样肽在单体、寡聚体和纤维状状态下的原子尺度和粗粒度模拟研究。特别强调了在原子细节水平上表征无序（多）肽的构象空间及其聚集所面临的挑战。我们讨论了比较模拟结果和实验数据的困难，并提出了新的模拟研究，以阐明与淀粉样疾病相关的聚集过程。
