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, Lihua ; Shi, Junyou ; Liu, Yongjun | |
2012-08-01 | |
发表期刊 | JOURNAL OF MOLECULAR MODELING
![]() ![]() |
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. |
文献类型 | 期刊论文 |
条目标识符 | http://210.75.249.4/handle/363003/21576 |
专题 | 中国科学院西北高原生物研究所 |
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, Song, T; Zhang, FP; Liu, YM; Wu, ZW; Suo, YR.Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium tuberculosis protein tyrosine phosphatase MptpB,JOURNAL OF MOLECULAR MODELING,2012,18(8):3847-3856,2012. |
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. |
MLA | Dong, Lihua,et al."Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium tuberculosis protein tyrosine phosphatase MptpB".JOURNAL OF MOLECULAR MODELING (2012). |
条目包含的文件 | 条目无相关文件。 |
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。
修改评论