辽宁大学学报（自然科学版）2025，Vol.52Issue(3)：261-270,10.
人胱抑素C、组织蛋白酶B和β淀粉样肽之间相互作用的分子对接及动力学模拟研究
Molecular Docking and Kinetic Simulation of the Interaction Between Human Cystatin C,Cathepsin B and Amyloid-Beta Peptide
摘要
Abstract
Amyloid-beta peptide(Aβ),cathepsin B(CatB),and human cystatin C(HCC)are three proteins associated with Alzheimer's disease(AD).Aβ can form aggregates in the brain,and these aggregates(oligomers and fibers)have neurotoxic effects.CatB is a cysteine protease present in the lysosome,and it participates in intracellular protein degradation and other processes.HCC is a protease inhibitor that regulates the activity of cysteine proteases such as CatB.The interaction among Aβ,HCC,and Cat B in vivo is a complex and dynamic process that is influenced by various factors,including physiological conditions and progressions of disease.Based on the study of molecular docking and dynamics of the interaction among three proteins related to AD,the possible encounter scenario of three proteins in the neural tissue fluid of patients with advanced AD were simulated using molecular docking analysis.First,HCC and Aβ were docked together and the most stable structure of the HCC-Aβ complex was used to dock as a whole protein with CatB.The HCC-Aβ complex and CatB were then docked using the HDOCK and ZDOCK program.The results showed that the free energies(Delta G)of the most stable of HCC-Aβ-CatB complexes in the HDOCK and ZDOCK program were-123.5 kJ/mol and-154.5 kJ/mol.Finally,molecular dynamics simulation was employed to simulate Complex 1 predicted by ZDOCK program over 100 ns timescale.The simulation revealed that after approximately 37.8 ns,the system reached a relatively stable state indicating that the complex formed by CatB,HCC,and Aβ could achieve stability.The results of this study could provide a certain theoretical basis for the scientific hypothesis that HCC may play a role in the early stage of AD,while CatB will play a major role in the later stage of AD.关键词
人胱抑素C/组织蛋白酶B/β淀粉样肽/分子对接/分子动力学模拟Key words
human cystatin C/cathepsin B/amyloid-beta peptide/molecular docking/molecular dynamics simulation分类
生物工程引用本文复制引用
何剑为,宋洪健,陈香梅,王静茹,单旭,崔燚,陈明月..人胱抑素C、组织蛋白酶B和β淀粉样肽之间相互作用的分子对接及动力学模拟研究[J].辽宁大学学报（自然科学版）,2025,52(3):261-270,10.基金项目
蒙医药研发工程教育部重点实验室开放课题项目(MDK2023064) （MDK2023064）
辽宁省教育厅高校基本科研项目(LJKMZ20220448) （LJKMZ20220448）
国家自然科学基金项目(31670103) （31670103）
