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Exploring the mechanism of the PTP1B inhibitors by molecular dynamics and experimental study

文献类型：期刊论文

作者Zhao, Tian-Tian1; Hu, Hao-Jie1; Gao, Li-Xin1,2; Zhou, Yu-Bo2; Zhu, Yun-Long3; Zhang, Chun1; Li, Jia2; Wang, Wen-Long1
刊名JOURNAL OF MOLECULAR GRAPHICS & MODELLING
出版日期2023-12-01
卷号125页码:12
ISSN号1093-3263
关键词Protein tyrosine phosphatases inhibitors PTP1B inhibitors Mechanism study Molecular dynamics
DOI10.1016/j.jmgm.2023.108585
通讯作者Zhu, Yun-Long(sequoia113847@163.com) ; Zhang, Chun(zhangchun@jiangnan.edu.cn) ; Li, Jia(jli@simm.ac.cn) ; Wang, Wen-Long(wenlongwang@jiangnan.edu.cn)
英文摘要Protein tyrosine phosphatase 1B (PTP1B) has proven to be an attractive target for the treatment of cancer, diabetes and other diseases. Although many PTP1B inhibitors with various scaffolds have been developed, there is still a lack of PTP1B inhibitor with high specificity and acceptable pharmacological properties. Therefore, it is urgent to develop more methods to explore complex action mode of PTP1B and ligands for designing ideal PTP1B modulators. In this work, we developed a potential molecular dynamics (MD) analytic mode to analyze the mechanism of active compounds 6a and 6e against PTP1B from different perspectives, including the stable ability, interactions and binding site of ligand and protein, the binding energy, relative movement between residues and changes in protein internal interactions. The simulated results demonstrated that compound 6a bound more stably to the active pocket of PTP1B than 6e due to its smaller molecular volume (326 & ANGS;3), matched electronegativity, and enhanced the positive correlation motion of residues, especially for WPD loop and P loop. Lastly, compound 6a as a competitive inhibitor for PTP1B was verified by enzyme kinetic assay. This work successfully studied the mechanism of compound 6a against PTP1B from various aspects, enriched the analysis of interaction mode between PTP1B and inhibitors. In summary, we hope that this work could provide more theoretical information for designing and developing more novel and ideal PTP1B inhibitors in the future.
WOS关键词TYROSINE-PHOSPHATASE 1B ; BIOLOGICAL EVALUATION ; FREE-ENERGY ; INSULIN-RECEPTOR ; PROTEIN BINDING ; DOCKING ; IDENTIFICATION ; PERFORMANCE ; DERIVATIVES ; ACID
资助项目National Natural Science Foundation of China[21772068] ; National Natural Science Foundation of China[JUSRP121065] ; Fundamental Research Funds for the Central Universities[JSSCBS20210848] ; High Level Personnel Project of Jiangsu Province ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences in Shanghai ; School of Biotechnology in Jiangnan University ; [22277043]
WOS研究方向Biochemistry & Molecular Biology ; Computer Science ; Crystallography ; Mathematical & Computational Biology
语种英语
出版者ELSEVIER SCIENCE INC
WOS记录号WOS:001053183000001
源URL[http://119.78.100.183/handle/2S10ELR8/307007]  
专题新药研究国家重点实验室
通讯作者Zhu, Yun-Long; Zhang, Chun; Li, Jia; Wang, Wen-Long
作者单位1.Jiangnan Univ, Sch Life Sci & Hlth Engn, Wuxi 214122, Jiangsu, Peoples R China
2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
3.Jiangnan Univ, Wuxi Maternal & Child Hlth Hosp, Wuxi Sch Med, Wuxi 214002, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714		 Zhao, Tian-Tian,Hu, Hao-Jie,Gao, Li-Xin,et al. Exploring the mechanism of the PTP1B inhibitors by molecular dynamics and experimental study[J]. JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2023,125:12.
APA Zhao, Tian-Tian.,Hu, Hao-Jie.,Gao, Li-Xin.,Zhou, Yu-Bo.,Zhu, Yun-Long.,...&Wang, Wen-Long.(2023).Exploring the mechanism of the PTP1B inhibitors by molecular dynamics and experimental study.JOURNAL OF MOLECULAR GRAPHICS & MODELLING,125,12.
MLA Zhao, Tian-Tian,et al."Exploring the mechanism of the PTP1B inhibitors by molecular dynamics and experimental study".JOURNAL OF MOLECULAR GRAPHICS & MODELLING 125(2023):12.

入库方式： OAI收割

来源：上海药物研究所

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