胆固醇酯转移蛋白天然产物抑制剂虚拟筛选和分子动力学模拟验证

Virtual screening and molecular dynamics simulation verification of cholesterol ester transfer protein from natural product inhibitors

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中文摘要：目的开发胆固醇酯转移蛋白(CETP)的天然产物抑制剂.方法采用计算机辅助技术,对高通量筛选天然产物数据库L6000 分别进行3 个精度梯度的分子对接、结合自由能计算、分子动力学模拟(MD模拟)等多轮虚拟筛选的策略,从中筛选CETP抑制剂.结果共筛选得到 19 个候选化合物,其中前 3 位化合物分别为肉苁蓉苷A、茶黄素、丹酚酸B二甲酯,结合模式分析显示上述化合物与靶标活性口袋之间形成了较强的相互作用;MD模拟的参数也证实上述蛋白-配体复合物结合的稳定性.结论肉苁蓉苷A、茶黄素、丹酚酸B二甲酯可作为CETP抑制剂的先导化合物.

外文摘要：Objective To develop natural product inhibitors of cholesterol ester transfer protein(CETP).Methods By using computer-aided technology,the high-throughput natural product database L6000 was screened for CETP inhibitors by multi-round virtual screening strategies such as molecular docking with three precision gradients,combined free energy calculation and molecular dynamics simulation(MD simulation).Results A total of 19 candidate compounds were screened,of which the first three compounds were cistanosideA,theaflavin and dimethyllithospermate B.Binding mode analysis showed that there was a strong interaction between the above compounds and the active pocket of the target,and the MD simulation parameters also confirmed the stability of the protein-ligand complex mentioned above.Conclution CistanosideA,theaflavin,and dimethyllithospermate B can be used as the lead compounds of possible CETP inhibitors.

外文关键词：

CETP proteindyslipidemianatural compoundsmall molecular inhibitorsvirtual screeningmolecular dockingmolecular dynamics simulationcistanoside Atheaflavindimethyllithospermate B

作者：

缪晓帆、李碧霞、尚文斌

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作者单位：

南京中医药大学附属医院心内科,江苏南京 210029

南京中医药大学第一临床医学院代谢病中医研究重点实验室,江苏南京 210023

南京中医药大学附属医院内分泌科,江苏南京 210029

关键词：

开发胆固醇酯转移蛋白血脂异常天然化合物小分子抑制剂虚拟筛选分子对接分子动力学模拟肉苁蓉苷A 茶黄素丹酚酸B二甲酯

出版年：

2024

DOI：

10.7501/j.issn.1674-5515.2024.12.004

现代药物与临床

天津药物研究院,中国药学会

现代药物与临床

CSTPCD

影响因子：1.179

ISSN：1674-5515

年,卷(期)：2024.39(12)