A Computational Study on Thiourea Analogs as Potent MK-2 Inhibitors
文献类型：期刊论文
| 作者 | Hao, Ming1; Ren, Hong2,3; Luo, Fang4; Zhang, Shuwei1; Qiu, Jieshan1; Ji, Mingjuan4; Si, Hongzong5,6; Li, Guohui3 |
| 刊名 | international journal of molecular sciences
 |
| 出版日期 | 2012-06-01 |
| 卷号 | 13期号:6页码:7057-7079 |
| 关键词 | 3D-QSAR molecular dynamics MK-2 inhibitors CoMFA CoMSIA |
| ISSN号 | 1661-6596 |
| 产权排序 | 3,2 |
| 通讯作者 | qiujieshan ; 李国辉 |
| 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. |
| WOS标题词 | science & technology ; physical sciences |
| 学科主题 | 物理化学 |
| 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 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000306188700032 |
| 公开日期 | 2013-10-11 |
| 源URL | [http://159.226.238.44/handle/321008/117984]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 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.,...&Li, Guohui.(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. |
入库方式： OAI收割
来源：大连化学物理研究所
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。