Knowledge Management System of Northwest Institute of Plateau Biology, CAS
| Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium tuberculosis protein tyrosine phosphatase MptpB | |
| Dong, Lihua1,2,3; Shi, Junyou1; Liu, Yongjun1 | |
| 2012-08-01 | |
| 发表期刊 | JOURNAL OF MOLECULAR MODELING
 |
| ISSN | 1610-2940 |
| 卷号 | 18期号:8页码:3847-3856 |
| 文章类型 | Article |
| 摘要 | MptpB is an essential secreted virulence factor for M. tuberculosis. Inhibition of MptpB impairs mycobacterial survival in host macrophages and thus helps reduce tuberculosis infections. However, the binding mode of the biphenyl inhibitors, which are known as some of the most potent MptpB inhibitors, remains unclear. In this study, to understand the interactions between biphenyl inhibitors and MptpB, docking and molecular dynamics simulations were carried out using AutoDock and GROMACS softwares. Calculation results show that all the biphenyl inhibitors can be docked to the binding site of MptpB, with the acid warheads forming a hydrogen bond network at the active site. But the binding modes of other terminals of these inhibitors are different. The cyclohexyl and trifluoromethyl substituents at R1 and R2 sites are necessary for the inhibitors to adopt their double-site binding mechanism. The estimated binding affinities are basically consistent with the experimental results. MD simulations show that these binding complexes display different stability.; MptpB is an essential secreted virulence factor for M. tuberculosis. Inhibition of MptpB impairs mycobacterial survival in host macrophages and thus helps reduce tuberculosis infections. However, the binding mode of the biphenyl inhibitors, which are known as some of the most potent MptpB inhibitors, remains unclear. In this study, to understand the interactions between biphenyl inhibitors and MptpB, docking and molecular dynamics simulations were carried out using AutoDock and GROMACS softwares. Calculation results show that all the biphenyl inhibitors can be docked to the binding site of MptpB, with the acid warheads forming a hydrogen bond network at the active site. But the binding modes of other terminals of these inhibitors are different. The cyclohexyl and trifluoromethyl substituents at R1 and R2 sites are necessary for the inhibitors to adopt their double-site binding mechanism. The estimated binding affinities are basically consistent with the experimental results. MD simulations show that these binding complexes display different stability. |
| 关键词 | Tyrosine Phosphatase b Biphenyl Inhibitor Interaction Molecular Docking Molecular Dynamics Simulation |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences ; Technology |
| 关键词[WOS] | BIOLOGY-ORIENTED SYNTHESIS ; ACTIVE-SITE ; PTPB ; IDENTIFICATION ; SIMULATIONS ; MACROPHAGES ; DISCOVERY ; DOCKING ; IMPAIRS ; POTENT |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Chemistry ; Computer Science |
| WOS类目 | Biochemistry & Molecular Biology ; Biophysics ; Chemistry, Multidisciplinary ; Computer Science, Interdisciplinary Applications |
| WOS记录号 | WOS:000307276900033 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://210.75.249.4/handle/363003/3634 |
| 专题 | 中国科学院西北高原生物研究所 |
| 作者单位 | 1.Chinese Acad Sci, NW Inst Plateau Biol, Key Lab Adaptat & Evolut Plateau Biota, Xining 810001, Qinghai, Peoples R China 2.Taishan Med Univ, Sch Chem Engn, Tai An 271000, Shandong, Peoples R China 3.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Dong, Lihua,Shi, Junyou,Liu, Yongjun. Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium tuberculosis protein tyrosine phosphatase MptpB[J]. JOURNAL OF MOLECULAR MODELING,2012,18(8):3847-3856. |
| APA | Dong, Lihua,Shi, Junyou,&Liu, Yongjun.(2012).Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium tuberculosis protein tyrosine phosphatase MptpB.JOURNAL OF MOLECULAR MODELING,18(8),3847-3856. |
| MLA | Dong, Lihua,et al."Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium tuberculosis protein tyrosine phosphatase MptpB".JOURNAL OF MOLECULAR MODELING 18.8(2012):3847-3856. |
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