Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics

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	Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics
	Ling, Baoping 1; Dong, Lihua 2,3; Zhang, Rui 2; Wang, Zhiguo 2; Liu, Yongjun 1,2; Liu, Chengbu 1
	2010-11-01
发表期刊	JOURNAL OF MOLECULAR GRAPHICS & MODELLING
ISSN	1093-3263
卷号	29 期号:3 页码:354-362
文章类型	Article
摘要	X-linked IAP can bind caspase-9 and inhibit its activity. Mitochondrial protein Smac/DIABLO can also interact with XIAP and relieve the inhibition on caspase-9 to induce apoptosis. A series of artificial Smac mimetics have been used to mimic the Smac N-terminal tetrapeptide AVPI to bind to XIAP-BIR3, but these structural diverse mimetics exhibited distinct binding affinities. To get an insight into the binding nature and optimize the structures, molecular docking and dynamics simulations were used to study the binding of XIAP-BIR3 with three groups of Smac mimetics. The docking results reveal that these Smac mimetics anchored on the surface groove of XIAP-BIR3 and superimposed well with AVPI. The modifications on the seven-membered ring of bicyclic core segment do not strengthen the binding affinity, while a benzyl introduced to the five-membered ring is favorable to the binding. Molecular dynamics simulations on three typical systems show that these complexes are very stable. Hydrogen bonds between the bicyclic core segment and Thr308 play critical roles in maintaining the stability of complex. The binding free energies calculated by MM_PBSA method are consistent with the experimental results. (C) 2010 Elsevier Inc. All rights reserved.; X-linked IAP can bind caspase-9 and inhibit its activity. Mitochondrial protein Smac/DIABLO can also interact with XIAP and relieve the inhibition on caspase-9 to induce apoptosis. A series of artificial Smac mimetics have been used to mimic the Smac N-terminal tetrapeptide AVPI to bind to XIAP-BIR3, but these structural diverse mimetics exhibited distinct binding affinities. To get an insight into the binding nature and optimize the structures, molecular docking and dynamics simulations were used to study the binding of XIAP-BIR3 with three groups of Smac mimetics. The docking results reveal that these Smac mimetics anchored on the surface groove of XIAP-BIR3 and superimposed well with AVPI. The modifications on the seven-membered ring of bicyclic core segment do not strengthen the binding affinity, while a benzyl introduced to the five-membered ring is favorable to the binding. Molecular dynamics simulations on three typical systems show that these complexes are very stable. Hydrogen bonds between the bicyclic core segment and Thr308 play critical roles in maintaining the stability of complex. The binding free energies calculated by MM_PBSA method are consistent with the experimental results. (C) 2010 Elsevier Inc. All rights reserved.
关键词	Smac Mimetics Caspase-9 Xiap-bir3 Molecular Docking Molecular Dynamics Simulations Binding Free Energy
WOS标题词	Science & Technology ; Life Sciences & Biomedicine ; Technology ; Physical Sciences
关键词[WOS]	X-LINKED INHIBITOR ; MITOCHONDRIA-DERIVED ACTIVATOR ; MOLECULAR-DYNAMICS SIMULATION ; STRUCTURE-BASED DESIGN ; BINDING FREE-ENERGY ; APOPTOSIS PROTEIN ; STRUCTURAL BASIS ; CASPASE ACTIVATION ; CELL-DEATH ; XIAP
收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Computer Science ; Crystallography ; Mathematical & Computational Biology
WOS类目	Biochemical Research Methods ; Biochemistry & Molecular Biology ; Computer Science, Interdisciplinary Applications ; Crystallography ; Mathematical & Computational Biology
WOS记录号	WOS:000285402500007
引用统计	被引频次：5[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/1628
专题	中国科学院西北高原生物研究所
作者单位	1.Shandong Univ, Sch Chem & Chem Engn, Minist Educ, Key Lab Colloid & Interface Chem, Jinan 250100, Shandong, Peoples R China 2.Chinese Acad Sci, NW Inst Plateau Biol, Xining 810001, Qinghai, Peoples R China 3.Taishan Med Univ, Sch Chem & Chem Engn, Tai An 270000, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Ling, Baoping,Dong, Lihua,Zhang, Rui,et al. Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics[J]. JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2010,29(3):354-362.
APA	Ling, Baoping,Dong, Lihua,Zhang, Rui,Wang, Zhiguo,Liu, Yongjun,&Liu, Chengbu.(2010).Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics.JOURNAL OF MOLECULAR GRAPHICS & MODELLING,29(3),354-362.
MLA	Ling, Baoping,et al."Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics".JOURNAL OF MOLECULAR GRAPHICS & MODELLING 29.3(2010):354-362.