Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor
文献类型：期刊论文
| 作者 | Liu, GX; Tan, JZ; Niu, CY; Shen, JH ; Luo, XM; Shen, X; Chen, KX; Jiang, HL
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| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2006-01 |
| 卷号 | 27期号:1页码:100-110 |
| 关键词 | molecular dynamics simulation principal component analysis protein-tyrosine phosphatase 1B type 2 diabetes |
| ISSN号 | 1671-4083 |
| DOI | 10.1111/j.1745-7254.2006.00251.x |
| 文献子类 | Article |
| 英文摘要 | Aim: To investigate the dynamic properties of protein-tyrosine phosphatase (PTP) 1B and reveal the structural factors responsible for the high inhibitory potency and selectivity of the inhibitor SNA for PTP1B. Methods: We performed molecular dynamics (MD) simulations using a long time-scale for both PTP1B and PTP1B complexed with the inhibitor SNA, the most potent and selective PTP1B inhibitor reported to date. The trajectories were analyzed by using principal component analysis. Results: Trajectory analyses showed that upon binding the ligand, the flexibility of the entire PTP1B molecule decreases. The most notable change is the movement of the WPD-loop. Our simulation results also indicated that electrostatic interactions contribute more to PTP1B-SNA complex conformation than the van der Waals interactions, and that Lys41, Arg47, and Asp48 play important roles in determining the conformation of the inhibitor SNA and in the potency and selectivity of the inhibitor. Of these, Arg47 contributed most. These results were in agreement with previous experimental results. Conclusion: The information presented here suggests that potent and selective PTP1B inhibitors can be designed by targeting the surface residues, for example the region containing Lys41, Arg47, and Asp48, instead of the second phosphate binding site (besides the active phosphate binding site). |
| WOS关键词 | SELECTIVE INHIBITORS ; PTP1B INHIBITORS ; CRYSTAL-STRUCTURE ; FLEXIBLE LOOP ; POTENT ; DESCRIPTORS ; DISCOVERY ; ISOMERASE ; PROGRAM ; DESIGN |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000234427200010 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273694]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Liu, GX |
| 作者单位 | 1.Chinese Acad Sci, Ctr Drug Discovery & Design, State Key Lab Drug Res, Shanghai Inst Mat Med,Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, GX,Tan, JZ,Niu, CY,et al. Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor[J]. ACTA PHARMACOLOGICA SINICA,2006,27(1):100-110. |
| APA | Liu, GX.,Tan, JZ.,Niu, CY.,Shen, JH.,Luo, XM.,...&Jiang, HL.(2006).Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor.ACTA PHARMACOLOGICA SINICA,27(1),100-110. |
| MLA | Liu, GX,et al."Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor".ACTA PHARMACOLOGICA SINICA 27.1(2006):100-110. |
入库方式： OAI收割
来源：上海药物研究所
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