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Molecular Dynamics Simulations Based on 1-Phenyl-4-Benzoyl-1-Hydro-Triazole ERR alpha Inverse Agonists

文献类型：期刊论文

作者Gao, Zhipei1; Du, Yongli1; Sheng, Xiehuang2; Shen, Jingkang3
刊名INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
出版日期2021-04-01
卷号22期号:7页码:14
关键词ERRα inverse agonists 1-phenyl-4-benzoyl-1-hydro-triazole MD simulations
DOI10.3390/ijms22073724
通讯作者Du, Yongli(yldu@qlu.edu.cn) ; Sheng, Xiehuang(shengxiehuang@sdnu.edu.cn)
英文摘要Estrogen-related receptor alpha (ERR alpha), which is overexpressed in a variety of cancers has been considered as an effective target for anticancer therapy. ERR alpha inverse agonists have been proven to effectively inhibit the migration and invasion of cancer cells. As few crystalline complexes have been reported, molecular dynamics (MD) simulations were carried out in this study to deepen the understanding of the interaction mechanism between inverse agonists and ERR alpha. The binding free energy was analyzed by the MM-GBSA method. The results show that the total binding free energy was positively correlated with the biological activity of an inverse agonist. The interaction of the inverse agonist with the hydrophobic interlayer composed of Phe328 and Phe495 had an important impact on the biological activity of inverse agonists, which was confirmed by the decomposition of energy on residues. As Glu331 flipped and formed a hydrogen bond with Arg372 in the MD simulation process, the formation of hydrogen bond interaction with Glu331 was not a necessary condition for the compound to act as an inverse agonist. These rules provide guidance for the design of new inverse agonists.
资助项目National Natural Science Foundation of China[81872744] ; Natural Science Foundation of Shandong Province[ZR2019MH046]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000638642700001
出版者MDPI
源URL[http://119.78.100.183/handle/2S10ELR8/295240]  
专题新药研究国家重点实验室
通讯作者Du, Yongli; Sheng, Xiehuang
作者单位1.Qilu Univ Technol, Sch Chem & Chem Engn, Shandong Acad Sci, 3501 Da Xue Rd, Jinan 250353, Peoples R China
2.Shandong Normal Univ, Coll Chem Chem Engn & Mat Sci, 88 Wen Hua Dong Rd, Jinan 250014, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Gao, Zhipei,Du, Yongli,Sheng, Xiehuang,et al. Molecular Dynamics Simulations Based on 1-Phenyl-4-Benzoyl-1-Hydro-Triazole ERR alpha Inverse Agonists[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2021,22(7):14.
APA Gao, Zhipei,Du, Yongli,Sheng, Xiehuang,&Shen, Jingkang.(2021).Molecular Dynamics Simulations Based on 1-Phenyl-4-Benzoyl-1-Hydro-Triazole ERR alpha Inverse Agonists.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,22(7),14.
MLA Gao, Zhipei,et al."Molecular Dynamics Simulations Based on 1-Phenyl-4-Benzoyl-1-Hydro-Triazole ERR alpha Inverse Agonists".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22.7(2021):14.

入库方式： OAI收割

来源：上海药物研究所

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