γ-secretase is an intra-membrane aspartyl protease involved in the production of amyloid-β peptides. Aberrant cleavage of the 99-residue C-terminal fragment of the amyloid precursor protein leads to the formation of a 42-amino-acid isoform (Aβ42). Further oligomerization and aggregation of this isoform is implicated in the onset and progression of Alzheimer's disease. Recent elucidation of γ-secretase by cryo-electron microscopy techniques have opened a new horizon in the structural and dynamic characterization of the enzyme. Currently, only a few molecular dynamics studies have been carried out to explore the mechanism of substrate recognition and entry, or the transition between active and inactive states of the catalytic subunit. Herein, we briefly review the computational approaches and their most relevant findings. The general picture of the current GS simulation studies will open new questions to understand the behavior of the enzyme dynamics and explain the modulation mechanisms for the treatment of Alzheimer's disease.

γ-分泌酶是涉及淀粉样β肽生产的膜内天冬氨酰蛋白酶。淀粉样前体蛋白的99个残基的C-末端片段的异常切割导致形成42个氨基酸的同工型（Aβ42）。该同工型的进一步低聚和聚集与阿尔茨海默氏病的发作和发展有关。最近通过冷冻电子显微镜技术对γ-分泌酶的阐明为酶的结构和动态表征开辟了新的视野。当前，仅进行了少数分子动力学研究以探索底物识别和进入的机理，或催化亚基的活性和非活性状态之间的过渡。本文中，我们简要回顾了计算方法及其最相关的发现。