DICP OpenIR
学科主题物理化学
A Computational Study on Thiourea Analogs as Potent MK-2 Inhibitors
Hao, Ming1; Ren, Hong2,3; Luo, Fang4; Zhang, Shuwei1; Qiu, Jieshan1; Ji, Mingjuan4; Si, Hongzong5,6; Li, Guohui3; QiuJieshan; Li GH(李国辉)
关键词3d-qsar Molecular Dynamics Mk-2 Inhibitors Comfa Comsia
刊名INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2012-06-01
ISSN1661-6596
DOI10.3390/ijms13067057
13期:6页:7057-7079
收录类别SCI
文章类型Article
部门归属11
项目归属1106
产权排名3,2
WOS标题词Science & Technology ; Physical Sciences
类目[WOS]Chemistry, Multidisciplinary
研究领域[WOS]Chemistry
关键词[WOS]ACTIVATED PROTEIN-KINASE-2 MK-2 ; PROTEIN-KINASE 2 ; ALPHA CONVERTING-ENZYME ; MK2 INHIBITORS ; BENZOTHIOPHENE INHIBITORS ; MOLECULAR-DYNAMICS ; TIBO DERIVATIVES ; QSAR MODELS ; SELECTIVITY ; REGRESSION
英文摘要Mitogen-activated protein kinase-activated protein kinase 2 (MK-2) has been identified as a drug target for the treatment of inflammatory diseases. Currently, a series of thiourea analogs as potent MK-2 inhibitors were studied using comprehensive computational methods by 3D-QSAR, molecular docking and molecular dynamics simulations for a further improvement in activities. The optimal 3D models exhibit high statistical significance of the results, especially for the CoMFA results with r(ncv)(2), q(2) values of 0.974, 0.536 for the internal validation, and r(pred)(2), r(m)(2) values of 0.910, 0.723 for the external validation and Roy's index, respectively. In addition, more rigorous validation criteria suggested by Tropsha were also employed to check the built models. Graphic representation of the results, as contoured 3D coefficient plots, also provides a clue to the reasonable modification of molecules: (i) The substituent with a bulky size and electron-rich group at the C5 position of the pyrazine ring is required to enhance the potency; (ii) The H-bond acceptor group in the C3 position of the pyrazine ring is likely to be helpful to increase MK-2 inhibition; (iii) The small and electropositive substituent as a hydrogen bond donor of the C2 position in the oxazolone ring is favored; In addition, several important amino acid residues were also identified as playing an important role in MK-2 inhibition. The agreement between 3D-QSAR, molecular docking and molecular dynamics simulations also proves the rationality of the developed models. These results, we hope, may be helpful in designing novel and potential MK-2 inhibitors.
语种英语
WOS记录号WOS:000306188700032
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/117984
专题中国科学院大连化学物理研究所
通讯作者QiuJieshan; Li GH(李国辉)
作者单位1.Dalian Univ Technol, Dept Mat Sci & Chem Engn, Dalian 116023, Peoples R China
2.Shandong Univ, Sch Med, Qi Lu Hosp, Dept Ophthalmol, Jinan 250012, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116023, Peoples R China
4.Chinese Acad Sci, Grad Sch, Coll Chem & Chem Engn, Beijing 100049, Peoples R China
5.Qingdao Univ, Inst Computat Sci & Engn, Lab New Fibrous Mat & Modern Text, Growing Base State Key Lab, Qingdao 266071, Peoples R China
6.Lanzhou Univ, Dept Chem, Lanzhou 730000, Peoples R China
推荐引用方式
GB/T 7714
Hao, Ming,Ren, Hong,Luo, Fang,et al. A Computational Study on Thiourea Analogs as Potent MK-2 Inhibitors[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2012,13(6):7057-7079.
APA Hao, Ming.,Ren, Hong.,Luo, Fang.,Zhang, Shuwei.,Qiu, Jieshan.,...&李国辉.(2012).A Computational Study on Thiourea Analogs as Potent MK-2 Inhibitors.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,13(6),7057-7079.
MLA Hao, Ming,et al."A Computational Study on Thiourea Analogs as Potent MK-2 Inhibitors".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 13.6(2012):7057-7079.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
2012ovGJMiuqPv.PDF(1362KB) 开放获取--请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Hao, Ming]的文章
[Ren, Hong]的文章
[Luo, Fang]的文章
百度学术
百度学术中相似的文章
[Hao, Ming]的文章
[Ren, Hong]的文章
[Luo, Fang]的文章
必应学术
必应学术中相似的文章
[Hao, Ming]的文章
[Ren, Hong]的文章
[Luo, Fang]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

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。