Mousseau Normand, Derreumaux Philippe
Departement de physique, Universite de Montreal, Case postale 6128, succursale centre-ville, Montreal, (Quebec), Canada H3C 3J7.
Front Biosci. 2008 May 1;13:4495-516. doi: 10.2741/3019.
Human diseases, such as Alzheimer's and Creutzfeldt-Jakob's are associated with misfolding and aggregation of specific proteins into amyloid fibrils sharing a generic cross-beta structure. The self-assembly process is complex, but once a nucleus is formed, rapid fibril formation occurs. Insight into the structures of the oligomers during the lag phase, varying between hours and days, is very difficult experimentally because these species are transient, and numerically using all-atom molecular dynamics because the time scale explored is on the order of 10-100 ns. It is therefore important to develop simplified protein models and alternative methods to sample more efficiently the conformational space. In the past few years, we have developed the activation-relaxation technique (ART nouveau) coupled to the OPEP coarse-grained force field. This review reports the application of ART-OPEP on protein folding and aggregation.
人类疾病，如阿尔茨海默病和克雅氏病，与特定蛋白质错误折叠并聚集成具有通用交叉β结构的淀粉样纤维有关。自组装过程很复杂，但一旦形成核，就会迅速形成纤维。在滞后阶段（持续数小时到数天不等）洞察低聚物的结构，通过实验很难实现，因为这些物种是瞬态的；通过全原子分子动力学进行数值模拟也很难，因为探索的时间尺度在10 - 100纳秒量级。因此，开发简化的蛋白质模型和替代方法以更有效地采样构象空间很重要。在过去几年中，我们开发了与OPEP粗粒化力场相结合的激活 - 弛豫技术（ART nouveau）。本综述报告了ART - OPEP在蛋白质折叠和聚集方面的应用。
