基于分子对接和表面等离子体共振技术筛选肉苁蓉复方制剂中AChE抑制剂的研究

doi:10.3969/j.issn.1004-616x.2023.05.004

癌变·畸变·突变 ›› 2023, Vol. 35 ›› Issue (5): 349-354,359.doi: 10.3969/j.issn.1004-616x.2023.05.004

基于分子对接和表面等离子体共振技术筛选肉苁蓉复方制剂中AChE抑制剂的研究

龚福恺¹, 刘佳丽², 张石蕾³

1. 新疆维吾尔自治区人民医院药学部, 新疆乌鲁木齐 830001;
2. 新疆医科大学药学院, 新疆乌鲁木齐 830017;
3. 新疆医科大学公共卫生学院, 新疆乌鲁木齐 830017

收稿日期:2023-07-10 修回日期:2023-09-15 发布日期:2023-10-13
通讯作者: 张石蕾
作者简介:龚福恺,E-mail:gfkfk@163.com。
基金资助:
新疆维吾尔自治区自然科学基金(2021D01C286)；新疆维吾尔自治区大学生创新创业计划项目(S202210760191X)

Discovery of AChE inhibitor in Cistanche tubulosa compound based on molecular docking and surface plasmon resonance

GONG Fukai¹, LIU Jiali², ZHANG Shilei³

1. Department of Pharmacy, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi 830001;
2. School of Pharmacy, Xinjiang Medical University, Urumqi 830017;
3. School of Public Health, Xinjiang Medical University, Urumqi 830017, Xinjiang, China

Received:2023-07-10 Revised:2023-09-15 Published:2023-10-13

摘要/Abstract

摘要： 目的： 虚拟筛选肉苁蓉复方制剂中潜在的乙酰胆碱酯酶(AChE)小分子抑制剂，为发现新型AChE抑制剂提供参考。方法： 基于中药系统药理学技术平台(TCMSP)及文献检索建立肉苁蓉复方制剂即肉苁蓉、人参和黄芪虚拟筛选的数据库，运用Rosetta软件进行Glide分子对接，利用围绕AChE受体活性位点的氨基酸残基形成一个大范围的Box，应用不同类型的成分作为探针进行扫描，计算格点能量进行能量排名，之后对配体在Box范围内进行构象搜索，根据配体的不同构象、方向、位置及能量进行评分，对结果进行排序，并最终采用表面等离子共振(SPR)技术对主要活性成分和AChE蛋白进行结合力验证。结果： AChE蛋白与肉苁蓉、人参和黄芪中挑选出来的典型性先导化合物结合模式以及结合能量均较好。在所有化合物分子对接体系中，肉苁蓉能量评分在-9.397~-0.858 kcal/mol之间；人参能量评分在-9.929~-0.211 kcal/mol之间；黄芪能量评分在-9.408~-1.555 kcal/mol之间；所有化合物对接小分子能量均小于-7.0 kcal/mol。SPR亲和力验证结果发现，槲皮素、山奈酚和染料木素均可与AChE蛋白显示出较好的结合力。结论： 基于分子对接技术筛选出肉苁蓉复方制剂中潜在的AChE抑制剂，结合SPR技术验证了AChE蛋白与活性成分之间良好的亲和力。

关键词: 乙酰胆碱酯酶, 肉苁蓉复方制剂, 分子对接虚拟筛选, 表面等离子体共振

Abstract: OBJECTIVE: Virtual screening of potential small molecule inhibitors of acetylcholinesterase (AChE) in Cistanche tubulosa compound preparations,while providing reference for the discovery of new AChE inhibitors. METHODS: A virtual screening database of Cistanche tubulosa, ginseng and astragalus was established based on the traditional Chinese medicine system pharmacology technology platform (TCMSP) and literature retrieval. The Glide molecule was docked by Rosetta software,and a wide range of Box was formed by using the amino acid residues around the active site of AChE receptor. Different types of components were used as probes to scan, and the lattice energy was calculated for energy ranking. After that, conformation of the ligand in the range of Box was searched,and the results were scored according to the different conformation, direction,position and energy of the ligand. Finally,the SPR technology was used to verify the binding force of the main active components and AChE protein. RESULTS: The binding mode and binding energy of AChE protein to the typical lead compounds selected from each system were good. In the molecular docking system of all compounds, Cistanche tubulosa energy scored between -9.397~-0.858 kcal/mol, ginseng energy score between -9.929~-0.211 kcal/mol and astragalus energy scored between -9.408~-1.555 kcal/mol. The docking energies of all compounds were less than -7.0 kcal/mol. The results of SPR affinity test showed that quercetin, kaempferol and genistein all showed good binding ability to AChE protein. CONCLUSION: The presence of AChE inhibitors in Cistanche tubulosa compound preparation was screened based on molecular docking technique, and the good affinity between AChE protein and active components was verified by SPR technique.

Key words: acetylcholinesterase, Cistanche tubulosa compound preparation, molecular docking virtual screening, surface plasmon resonance

中图分类号:

R285.5

龚福恺, 刘佳丽, 张石蕾. 基于分子对接和表面等离子体共振技术筛选肉苁蓉复方制剂中AChE抑制剂的研究[J]. 癌变·畸变·突变, 2023, 35(5): 349-354,359.

GONG Fukai, LIU Jiali, ZHANG Shilei. Discovery of AChE inhibitor in Cistanche tubulosa compound based on molecular docking and surface plasmon resonance[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(5): 349-354,359.

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基于分子对接和表面等离子体共振技术筛选肉苁蓉复方制剂中AChE抑制剂的研究

Discovery of AChE inhibitor in Cistanche tubulosa compound based on molecular docking and surface plasmon resonance

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