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

	Theoretical studies on the interaction of biphenyl inhibitors with Mycobacterium tuberculosis protein tyrosine phosphatase MptpB
	Dong, Lihua 1,2,3; Shi, Junyou 1; Liu, Yongjun 1
刊名	journal of molecular modeling
	2012-08-01
卷号	18 期号:8 页码:3847-3856
关键词	Tyrosine phosphatase B Biphenyl inhibitor Interaction Molecular docking Molecular dynamics simulation
ISSN号	1610-2940
中文摘要	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.
英文摘要	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.
WOS标题词	science & technology ; life sciences & biomedicine ; physical sciences ; technology
类目[WOS]	biochemistry & molecular biology ; biophysics ; chemistry, multidisciplinary ; computer science, interdisciplinary applications
研究领域[WOS]	biochemistry & molecular biology ; biophysics ; chemistry ; computer science
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记录号	WOS:000307276900033
公开日期	2013-03-15
内容类型	期刊论文
源URL	[http://ir.nwipb.ac.cn/handle/363003/3634]
专题	西北高原生物研究所_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.