STUDY ON THE INTERACTIONS OF Smac MIMETICS WITH XIAP-BIR3 DOMAIN BY DOCKING AND MOLECULAR DYNAMICS SIMULATIONS

	STUDY ON THE INTERACTIONS OF Smac MIMETICS WITH XIAP-BIR3 DOMAIN BY DOCKING AND MOLECULAR DYNAMICS SIMULATIONS
	Ling, Baoping ; Zhang, Rui ; Wang, Zhiguo ; Liu, Yongjun ; Liu, Chengbu
刊名	JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY ; Ling, BP; Zhang, R; Wang, ZG; Liu, YJ; Liu, CB.STUDY ON THE INTERACTIONS OF Smac MIMETICS WITH XIAP-BIR3 DOMAIN BY DOCKING AND MOLECULAR DYNAMICS SIMULATIONS,JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY,2010,9(4):797-812
	2010-08-01
英文摘要	Upon receiving an apoptotic stimulus, the mature mitochondrial protein second mitochondria-derived activator of caspases (Smac)direct IAP-binding protein with low PI (DIABLO), which could be released from mitochondria into the cytosol together with cytochrome C, specifically binds to inhibitor of apoptosis proteins (IAPs) and relieves the inhibitory effect of caspase, thus promotes cell death. Some artificial small molecules (called Smac mimetics) can mimic the N-terminal four residues Ala1-Val2-Pro3-Ile4 (AVPI) sequence of mitochondrial protein Smac, and competitively bind to X-linked inhibitor of apoptosis protein baculoviral IAP repeats (XIAP-BIR3) domain with caspase-9, which leads to the removal of the inhibition of caspase-9 by XIAP and induce apoptosis. To gain an insight into the nature of XIAP-BIR3 domain recognizing Smac mimetics, we used docking and molecular dynamics simulations methods to study four representative Smac mimetics. The docking results show that the orientations of these backbones of ligands are identical with that of AVPI in the binding pocket. Each ligand corresponds to two competitive conformations, which are called extended and bended conformations. The results of molecular dynamics simulations show that the extended conformation is more stable, and the calculations of energy decomposition reveal that the residue Thr308 makes the strongest interaction with XIAP-BIR3. In addition, Asp309, Glu314, and Trp323 are indispensable for XIAP-BIR3 recognizing and binding Smac mimetics.; Upon receiving an apoptotic stimulus, the mature mitochondrial protein second mitochondria-derived activator of caspases (Smac)direct IAP-binding protein with low PI (DIABLO), which could be released from mitochondria into the cytosol together with cytochrome C, specifically binds to inhibitor of apoptosis proteins (IAPs) and relieves the inhibitory effect of caspase, thus promotes cell death. Some artificial small molecules (called Smac mimetics) can mimic the N-terminal four residues Ala1-Val2-Pro3-Ile4 (AVPI) sequence of mitochondrial protein Smac, and competitively bind to X-linked inhibitor of apoptosis protein baculoviral IAP repeats (XIAP-BIR3) domain with caspase-9, which leads to the removal of the inhibition of caspase-9 by XIAP and induce apoptosis. To gain an insight into the nature of XIAP-BIR3 domain recognizing Smac mimetics, we used docking and molecular dynamics simulations methods to study four representative Smac mimetics. The docking results show that the orientations of these backbones of ligands are identical with that of AVPI in the binding pocket. Each ligand corresponds to two competitive conformations, which are called extended and bended conformations. The results of molecular dynamics simulations show that the extended conformation is more stable, and the calculations of energy decomposition reveal that the residue Thr308 makes the strongest interaction with XIAP-BIR3. In addition, Asp309, Glu314, and Trp323 are indispensable for XIAP-BIR3 recognizing and binding Smac mimetics.
内容类型	期刊论文
源URL	[http://ir.nwipb.ac.cn//handle/363003/1658]
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
推荐引用方式 GB/T 7714	Ling, Baoping,Zhang, Rui,Wang, Zhiguo,et al. STUDY ON THE INTERACTIONS OF Smac MIMETICS WITH XIAP-BIR3 DOMAIN BY DOCKING AND MOLECULAR DYNAMICS SIMULATIONS[J]. JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY, Ling, BP; Zhang, R; Wang, ZG; Liu, YJ; Liu, CB.STUDY ON THE INTERACTIONS OF Smac MIMETICS WITH XIAP-BIR3 DOMAIN BY DOCKING AND MOLECULAR DYNAMICS SIMULATIONS,JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY,2010,9(4):797-812,2010.
APA	Ling, Baoping,Zhang, Rui,Wang, Zhiguo,Liu, Yongjun,&Liu, Chengbu.(2010).STUDY ON THE INTERACTIONS OF Smac MIMETICS WITH XIAP-BIR3 DOMAIN BY DOCKING AND MOLECULAR DYNAMICS SIMULATIONS.JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY.
MLA	Ling, Baoping,et al."STUDY ON THE INTERACTIONS OF Smac MIMETICS WITH XIAP-BIR3 DOMAIN BY DOCKING AND MOLECULAR DYNAMICS SIMULATIONS".JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY (2010).