中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 药物发现与设计中心
Inhibiting mechanism of small molecule toward the p53-MDM2 interaction: A molecular dynamic exploration

文献类型：期刊论文

作者Chen, Jianzhong1,2; Wang, Jinan2; Pang, Laixue1; Zhu, Weiliang2
刊名CHEMICAL BIOLOGY & DRUG DESIGN
出版日期2018-10
卷号92期号:4页码:1763-1777
关键词hydrophobic contact scanning MM-GBSA p53-MDM2 interaction principal component analysis solvated interaction energy
ISSN号1747-0277
DOI10.1111/cbdd.13345
文献子类Article
英文摘要Disruption of the p53-MDM2 interaction has been an efficient strategy to renew the function of wild-type p53. In this work, molecular dynamic simulations, molecular mechanics-generalized Born surface area method, and principal component analysis were combined to probe interaction mechanism of inhibitors 2TZ, 2U0, 2U1, 2U5, 2U6, and 2U7 with MDM2. The rank of our current predicted binding free energies is in agreement with that of the experimental values. The results demonstrate that the introductions of thiazole and pyridine rings into 2TZ as well as the change in the orientation of inhibitors lead to the increase in the polar interactions of 2U0, 2U1, 2U5, 2U6, and 2U7 with MDM2 relative to 2TZ. The information derived from principal component analysis suggests that inhibitor bindings produce significant effect on the binding cleft of MDM2 and make the binding cleft wider and bigger so as to accommodate different type inhibitors. This study is looked forward to contributing theoretical hints for designs of potent inhibitors targeting the p53-MDM2 interaction.
WOS关键词PROTEIN-PROTEIN INTERACTIONS ; SOLVATED INTERACTION ENERGY ; BOUNDARY-ELEMENT METHOD ; STRUCTURE-BASED DESIGN ; BINDING FREE-ENERGIES ; PARTICLE MESH EWALD ; CONFORMATIONAL-CHANGES ; MDM2-MEDIATED UBIQUITINATION ; PEPTIDE INHIBITION ; P53 MUTATIONS
资助项目National Key Research and Development Program[2016YFA0502301] ; National Natural Science Foundation of China[21403283] ; National Natural Science Foundation of China[11274206] ; National Natural Science Foundation of China[81273435] ; National Natural Science Foundation of China[81573350] ; Shandong Province Key Research and Development Program[2016GGX102043] ; CAS Key Laboratory of Receptor Research[SIMM1706YKF-03] ; Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund[U1501501]
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000452242200005
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/279544]  
专题药物发现与设计中心
通讯作者Chen, Jianzhong; Wang, Jinan; Pang, Laixue
作者单位1.Shandong Jiaotong Univ, Sch Sci, Jinan 250014, Shandong, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Jianzhong,Wang, Jinan,Pang, Laixue,et al. Inhibiting mechanism of small molecule toward the p53-MDM2 interaction: A molecular dynamic exploration[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2018,92(4):1763-1777.
APA Chen, Jianzhong,Wang, Jinan,Pang, Laixue,&Zhu, Weiliang.(2018).Inhibiting mechanism of small molecule toward the p53-MDM2 interaction: A molecular dynamic exploration.CHEMICAL BIOLOGY & DRUG DESIGN,92(4),1763-1777.
MLA Chen, Jianzhong,et al."Inhibiting mechanism of small molecule toward the p53-MDM2 interaction: A molecular dynamic exploration".CHEMICAL BIOLOGY & DRUG DESIGN 92.4(2018):1763-1777.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。