College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Curr Med Chem. 2024;31(20):2855-2871. doi: 10.2174/0929867330666230409145247.
Tau dysfunction has a close association with many neurodegenerative diseases, which are collectively referred to as tauopathies. Neurofibrillary tangles (NFTs) formed by misfolding and aggregation of tau are the main pathological process of tauopathy. Therefore, uncovering the misfolding and aggregation mechanism of tau protein will help to reveal the pathogenic mechanism of tauopathies. Molecular dynamics (MD) simulation is well suited for studying the dynamic process of protein structure changes. It provides detailed information on protein structure changes over time at the atomic resolution. At the same time, MD simulation can also simulate various conditions conveniently. Based on these advantages, MD simulations are widely used to study conformational transition problems such as protein misfolding and aggregation. Here, we summarized the structural features of tau, the factors affecting its misfolding and aggregation, and the applications of MD simulations in the study of tau misfolding and aggregation.
tau 功能障碍与许多神经退行性疾病密切相关，这些疾病统称为 tau 病。tau 错误折叠和聚集形成的神经原纤维缠结（NFTs）是 tau 病的主要病理过程。因此，揭示 tau 蛋白的错误折叠和聚集机制将有助于揭示 tau 病的发病机制。分子动力学（MD）模拟非常适合研究蛋白质结构变化的动态过程。它提供了有关蛋白质结构随时间变化的原子分辨率的详细信息。同时，MD 模拟还可以方便地模拟各种条件。基于这些优势，MD 模拟广泛用于研究蛋白质错误折叠和聚集等构象转变问题。在这里，我们总结了 tau 的结构特征、影响其错误折叠和聚集的因素，以及 MD 模拟在 tau 错误折叠和聚集研究中的应用。
