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Covalent complexes of proteasome model with peptide aldehyde inhibitors MG132 and MG101: docking and molecular dynamics study
Zhang, Siwei; Shi, Yawei; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren; Zhang, Lihe
关键词Covalent docking Molecular dynamics Peptide aldehydes Proteasome Structure-activity relationship
刊名JOURNAL OF MOLECULAR MODELING
2009-12-01
DOI10.1007/s00894-009-0515-0
15期:12页:1481-1490
收录类别SCI
文章类型Article
WOS标题词Science & 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]MAMMALIAN 20S PROTEASOME ; SELECTIVE INHIBITORS ; ANGSTROM RESOLUTION ; PROTEIN ; DESIGN ; SYSTEM ; POTENT ; DEGRADATION ; MECHANISM ; PITUITARY
英文摘要

20S proteasome plays a critical role in the regulation of several important cellular processes and has drawn extensive interest in the field of anti-tumor research. Peptide aldehydes can inhibit the 20S proteasome activity by covalently binding to the active site of the beta subunits. In this work, covalent docking in conjunction with molecular dynamics (MD) simulation was used to explore the binding mode of MG132. Two conformations with the lowest docking energy were selected as the representative binding modes. One of the conformations was confirmed as a more reasonable binding mode by molecular dynamics simulations. The binding mode analysis revealed that a space demanding aromatic group with a short linker at the P4 site of the peptide aldehyde inhibitor would form favorable hydrophobic contacts with the neighboring subunit. A bulky substituent at the P2 position would also increase the binding stability by reducing water accessibility of the covalent bond. This study contributed to our understanding of the mechanism and structure-activity relationship of the peptide aldehyde inhibitors and may provide useful information for rational drug design.

语种英语
WOS记录号WOS:000270984200006
Citation statistics
Cited Times:17[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63305
Collection北京大学药学院
北京大学药学院_天然药物与仿生药物国家重点实验室
北京大学药学院_药物化学系
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
Recommended Citation
GB/T 7714
Zhang, Siwei,Shi, Yawei,Jin, Hongwei,et al. Covalent complexes of proteasome model with peptide aldehyde inhibitors MG132 and MG101: docking and molecular dynamics study[J]. JOURNAL OF MOLECULAR MODELING,2009,15(12):1481-1490.
APA Zhang, Siwei,Shi, Yawei,Jin, Hongwei,Liu, Zhenming,Zhang, Liangren,&Zhang, Lihe.(2009).Covalent complexes of proteasome model with peptide aldehyde inhibitors MG132 and MG101: docking and molecular dynamics study.JOURNAL OF MOLECULAR MODELING,15(12),1481-1490.
MLA Zhang, Siwei,et al."Covalent complexes of proteasome model with peptide aldehyde inhibitors MG132 and MG101: docking and molecular dynamics study".JOURNAL OF MOLECULAR MODELING 15.12(2009):1481-1490.
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