Study of a ligand complexed with Cdk2/Cdk4 by computer simulation
文献类型：期刊论文
| 作者 | Jiang, YJ; Zou, JW; Gui, CS |
| 刊名 | JOURNAL OF MOLECULAR MODELING
 |
| 出版日期 | 2005-11 |
| 卷号 | 11期号:6页码:509-515 |
| 关键词 | homology modeling molecular docking molecular dynamics MM-PBSA binding selectivity |
| ISSN号 | 1610-2940 |
| DOI | 10.1007/s00894-005-0263-8 |
| 文献子类 | Article |
| 英文摘要 | Cyclin-dependent kinases (Cdks) play important roles in the regulation of the cell cycle. Their inhibitors have entered clinical trials to treat cancer. Very recently, Davis et al. (Nat Struct Biol 9:745-749, 2002) have found a ligand NU6102, which has a high affinity with cyclin-dependent kinase 2 (K (i) =6 nM) but a low affinity with cyclin-dependent kinase 4 (K-i =1,600 nM). To understand the selectivity, we use homology modeling, molecular docking, molecular dynamics and free-energy calculations to analyze the interactions. A rational 3D model of the Cdk4-NU6102 complex is built. Asp86 is a key residue that recognizes NU6102 more effectively with Cdk2 rather than Cdk4. Good binding free energies are obtained. Energetic analysis reveals that van der Waals interaction and nonpolar contributions to solvent are favorable in the formation of complexes and the sulfonamide group of the ligand plays a crucial role for binding selectivity between Cdk2 and Cdk4. |
| WOS关键词 | DEPENDENT KINASE INHIBITORS ; FREE-ENERGIES ; MOLECULAR-DYNAMICS ; CDK4 INHIBITORS ; LIBRARY DESIGN ; CELL-CYCLE ; CANCER ; HYDRATION ; PROTEINS |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Chemistry ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000233482500009 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273783]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Jiang, YJ |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Discovery & Design, Shanghai 200031, Peoples R China 2.Zhejiang Univ, Ningbo Inst Technol, Key Lab Mol Design & Nutr Engn, Ningbo 315104, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, YJ,Zou, JW,Gui, CS. Study of a ligand complexed with Cdk2/Cdk4 by computer simulation[J]. JOURNAL OF MOLECULAR MODELING,2005,11(6):509-515. |
| APA | Jiang, YJ,Zou, JW,&Gui, CS.(2005).Study of a ligand complexed with Cdk2/Cdk4 by computer simulation.JOURNAL OF MOLECULAR MODELING,11(6),509-515. |
| MLA | Jiang, YJ,et al."Study of a ligand complexed with Cdk2/Cdk4 by computer simulation".JOURNAL OF MOLECULAR MODELING 11.6(2005):509-515. |
入库方式： OAI收割
来源：上海药物研究所
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