Structural Dynamics of Amyloid β Peptide Binding to Acetylcholine Receptor and Virtual Screening for Effective Inhibitors  

β淀粉样蛋白结合乙酰胆碱受体的结构动力学及抑制剂的虚拟筛选探究

作　　者：Yan-jun Hou Xuan Zheng Hong-mei Zhong Feng Chen Gui-vang Yan Kai-cong Cai 侯彦君;郑轩;钟红梅;陈峰;颜桂炀;蔡开聪(福建师范大学化学与材料学院,先进材料化工基础实验室,福州350007;宁德师范学院,福建省特色生物化工材料重点实验室,宁德352100;福建省理论与计算化学重点实验室,厦门361005;中国科学院化学研究所,北京国家分子科学实验室,北京100190)

机构地区：[1]College of Chemistry and Materials Science,Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering,Fuian Normal University,Fuzhou 350007,China [2]Fuijian Provincial Key Laboratory of Featured Biochemical and Chemical Materials,Ningde Normal University,Ningde 352100,China [3]Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry,Xiamen 361005,China [4]Beijing National Laboratory for Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China

出　　处：《Chinese Journal of Chemical Physics》2021年第3期323-333,I0048,共12页化学物理学报（英文）

基　　金：supported by the National Natural Science Foundation of China(No.21103021);the New Century Excellent Talent Project in University of Fujian Province,Opening Project of PCOSS,Xiamen University(No.201904)。

摘　　要：The interaction between Amyloid β(Aβ) peptide and acetylcholine receptor is the key for our understanding of how Aβ fragments block the ion channels within the synapses and thus induce Alzheimer’s disease.Here,molecular docking and molecular dynamics(MD)simulations were performed for the structural dynamics of the docking complex consisting of Aβ and α7-n ACh R(α7 nicotinic acetylcholine receptor),and the inter-molecular interactions between ligand and receptor were revealed.The results show that Aβ_(25-35) is bound toα7-n ACh R through hydrogen bonds and complementary shape,and the Aβ_(25-35) fragments would easily assemble in the ion channel of α7-n ACh R,then block the ion transfer process and induce neuronal apoptosis.The simulated amide-I band of Aβ_(25-35) in the complex is located at 1650.5 cm^(-1),indicating the backbone of Aβ_(25-35) tends to present random coil conformation,which is consistent with the result obtained from cluster analysis.Currently existing drugs were used as templates for virtual screening,eight new drugs were designed and semi-flexible docking was performed for their performance.The results show that,the interactions between new drugs and α7-n ACh R are strong enough to inhibit the aggregation of Aβ_(25-35) fragments in the ion channel,and also be of great potential in the treatment of Alzheimer’s disease.

关 键 词：Amyloidβpeptide Acetylcholine receptor Molecular dynamics simulation Molecular docking Virtual screening 

分 类 号：TQ460.1[化学工程—制药化工]