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Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations

文献类型：期刊论文

作者Yu, Zhe1,2; Ma, Yu-chi1; Ai, Jing1; Chen, Dan-qi1; Zhao, Dong-mei2; Wang, Xin1; Chen, Yue-lei1; Geng, Mei-yu1; Xiong, Bing1; Cheng, Mao-sheng2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2013-11
卷号34期号:11页码:1475-1483
关键词receptor tyrosine kinase type I c-Met inhibitor cancer quantum chemistry protein-ligand interaction symmetry-adapted perturbation theory (SAPT)
ISSN号1671-4083
DOI10.1038/aps.2013.85
文献子类Article
英文摘要Aim: To decipher the molecular interactions between c-Met and its type I inhibitors and to facilitate the design of novel c-Met inhibitors. Methods: Based on the prototype model inhibitor 1, four ligands with subtle differences in the fused aromatic rings were synthesized. Quantum chemistry was employed to calculate the binding free energy for each ligand. Symmetry-adapted perturbation theory (SAPT) was used to decompose the binding energy into several fundamental forces to elucidate the determinant factors. Results: Binding free energies calculated from quantum chemistry were correlated well with experimental data. SAPT calculations showed that the predominant driving force for binding was derived from a sandwich p-p interaction with Tyr-1230. Arg-1208 was the differentiating factor, interacting with the 6-position of the fused aromatic ring system through the backbone carbonyl with a force pattern similar to hydrogen bonding. Therefore, a hydrogen atom must be attached at the 6-position, and changing the carbon atom to nitrogen caused unfavorable electrostatic interactions. Conclusion: The theoretical studies have elucidated the determinant factors involved in the binding of type I inhibitors to c-Met.
WOS关键词PI-PI-INTERACTIONS ; PERTURBATION-THEORY ; SIGNALING PATHWAY ; CANCER-THERAPY ; SUBSTITUENTS ; DISPERSION ; SANDWICH ; RECEPTOR ; PROGRESS ; BENZENE
资助项目Program of Excellent Young Scientists of the Chinese Academy of Sciences[KSCX2-EW-Q-3-01] ; National Natural Science Foundation of China[81072580] ; "Interdisciplinary Cooperation Team" Program for Science and Technology Innovation of the Chinese Academy of Sciences[00000000]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:4966502
WOS记录号WOS:000326680500014
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/277400]  
专题药物化学研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药理学第一研究室
通讯作者Zhao, Dong-mei
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
2.Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Shenyang 110016, Peoples R China
推荐引用方式
GB/T 7714		 Yu, Zhe,Ma, Yu-chi,Ai, Jing,et al. Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations[J]. ACTA PHARMACOLOGICA SINICA,2013,34(11):1475-1483.
APA Yu, Zhe.,Ma, Yu-chi.,Ai, Jing.,Chen, Dan-qi.,Zhao, Dong-mei.,...&Shen, Jing-kang.(2013).Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations.ACTA PHARMACOLOGICA SINICA,34(11),1475-1483.
MLA Yu, Zhe,et al."Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations".ACTA PHARMACOLOGICA SINICA 34.11(2013):1475-1483.

入库方式： OAI收割

来源：上海药物研究所

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