Computational Studies on Acetylcholinesterases
文献类型：期刊论文
| 作者 | Xu, Yechun3 ; Cheng, Shanmei3; Sussman, Joel L.1,4; Silman, Israel2; Jiang, Hualiang3
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| 刊名 | MOLECULES
 |
| 出版日期 | 2017-08 |
| 卷号 | 22期号:8 |
| 关键词 | acetylcholinesterase computational modeling and simulation active-site gorge ligand trafficking oligomer catalytic reaction mechanism |
| ISSN号 | 1420-3049 |
| DOI | 10.3390/molecules22081324 |
| 文献子类 | Review |
| 英文摘要 | Functions of biomolecules, in particular enzymes, are usually modulated by structural fluctuations. This is especially the case in a gated diffusion-controlled reaction catalyzed by an enzyme such as acetylcholinesterase. The catalytic triad of acetylcholinesterase is located at the bottom of a long and narrow gorge, but it catalyzes the extremely rapid hydrolysis of the neurotransmitter, acetylcholine, with a reaction rate close to the diffusion-controlled limit. Computational modeling and simulation have produced considerable advances in exploring the dynamical and conformational properties of biomolecules, not only aiding in interpreting the experimental data, but also providing insights into the internal motions of the biomolecule at the atomic level. Given the remarkably high catalytic efficiency and the importance of acetylcholinesterase in drug development, great efforts have been made to understand the dynamics associated with its functions by use of various computational methods. Here, we present a comprehensive overview of recent computational studies on acetylcholinesterase, expanding our views of the enzyme from a microstate of a single structure to conformational ensembles, strengthening our understanding of the integration of structure, dynamics and function associated with the enzyme, and promoting the structure-based and/or mechanism-based design of new inhibitors for it. |
| WOS关键词 | ACTIVE-SITE GORGE ; MOLECULAR-DYNAMICS SIMULATIONS ; AB-INITIO QM/MM ; MULTIPLE DOCKING APPROACH ; MOUSE ACETYLCHOLINESTERASE ; TORPEDO-CALIFORNICA ; BROWNIAN DYNAMICS ; OMEGA-LOOP ; COVALENT INHIBITION ; COMPUTER-SIMULATION |
| 资助项目 | National Key R&D Program of China[2016YFA0502301] ; National Natural Science Foundation of China[81422047] ; National Natural Science Foundation of China[81661148046] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000408602900088 |
| 出版者 | MDPI AG |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272538]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Xu, Yechun |
| 作者单位 | 1.Weizmann Inst Sci, Israel Struct Prote Ctr, IL-76100 Rehovot, Israel; 2.Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Weizmann Inst Sci, Dept Struct Biol, IL-76100 Rehovot, Israel; |
| 推荐引用方式 GB/T 7714 | Xu, Yechun,Cheng, Shanmei,Sussman, Joel L.,et al. Computational Studies on Acetylcholinesterases[J]. MOLECULES,2017,22(8). |
| APA | Xu, Yechun,Cheng, Shanmei,Sussman, Joel L.,Silman, Israel,&Jiang, Hualiang.(2017).Computational Studies on Acetylcholinesterases.MOLECULES,22(8). |
| MLA | Xu, Yechun,et al."Computational Studies on Acetylcholinesterases".MOLECULES 22.8(2017). |
入库方式： OAI收割
来源：上海药物研究所
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