Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium tuberculosis protein tyrosine phosphatase MptpB

NWIPB OpenIR

	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 ; 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
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/363003/36864
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).