Molecular basis of cross-interactions between Aβ and Tau protofibrils probed by molecular simulations  

作　　者：Fufeng Liu Luying Jiang Jingcheng Sang Fuping Lu Li Li 

机构地区：[1]State Key Laboratory of Food Nutrition and Safety,Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education,Tianjin Key Laboratory of Industrial Microbiology,College of Biotechnology,Tianjin University of Science&Technology,Tianjin 300457,China [2]College of Marine and Environmental Science,Tianjin University of Science&Technology,Tianjin 300457,China

出　　处：《Chinese Journal of Chemical Engineering》2023年第3期173-180,共8页中国化学工程学报（英文版）

基　　金：funded by the National Natural Science Foundation of China (21908165 and 21878234);Regional Innovation System Project (21ZYQCSY00050)。

摘　　要：Amyloid β-protein(Aβ) and Tau, two common pathogenic proteins associated with Alzheimer’s disease(AD), cross-interact, and thus co-assemble into hybrid aggregates. However, molecular mechanism of the cross-interactions remains unclear. To explore the issue, docking and molecular dynamics(MD) simulations were coupled to study the cross-interactions between Aβ pentamer and Tau pentamer. Four stable hybrid decamer conformations including double layer, single layer, block, and part-in were obtained by protein-protein docking software HADDOCK 2.2. Then, MD simulations were used to explore the molecular mechanism of cross-interactions between Aβ pentamer and Tau pentamer. The results of MD simulations showed that the part-in structure was the most stable among all the above four representative ones. The binding energy between Aβ and Tau was about-759.77 kJ·mol-1in the part-in structure. Moreover, the part-in conformation would undergo conformational transition, which would improve its hydrophobicity and make the structure more compact. This work offers a structural understanding of cross-interactions between Aβ and Tau linked to AD.

关 键 词：Alzheimer’s disease Amyloidβ-protein Tau Cross-interactions Protein-protein docking Molecular dynamics simulation 

分 类 号：R749.16[医药卫生—神经病学与精神病学]