A computational analysis of interaction mechanisms of peptide and non-peptide inhibitors with MDMX based on molecular dynamics simulation

	A computational analysis of interaction mechanisms of peptide and non-peptide inhibitors with MDMX based on molecular dynamics simulation
	Cheng, Wei-yuan 2; Chen, Jian-zhong 1; Liang, Zhi-qiang 1; Li, Guo-hui 3; Yi, Chang-hong 1; Wang, Wei 1; Wang, Ke-yan 1
刊名	computational and theoretical chemistry
	2012-03-15
卷号	984 页码:43-50
关键词	MD simulation Computational alanine scanning MM-GBSA method p53-MDMX interaction Cross correlation analysis
ISSN号	2210-271x
通讯作者	chenjianzhong
产权排序	3,4
英文摘要	inhibition of p53-mdm2/mdmx interaction is considered to be a new approach to active wild type p53 in tumors. molecular dynamics simulation (md) coupled with molecular mechanics generalized born surface area (mm-gbsa) method were performed to probe the binding mechanisms of peptide and non-peptide inhibitors to mdmx. the results show that van der waals energy is a main force of the inhibitor-mdmx binding. we found that the peptide inhibitors should generate more interaction contacts with mdmx than the non-peptide inhibitors. computational alanine scanning and analysis of structure-affinity relation were used to predict the inhibitor-protein binding modes. the results show that six common residues met53, ile60, met61, tyr66, val92 and leu98 locate in the hot spot of the surface between inhibitors and mdmx. the analyses of dynamics properties suggest that the peptide inhibitors are in favor of the stability of the inhibitor-mdmx complex. we expect that this study can contribute significantly to the designs of the potent inhibitors targeting the p53-mdmx interaction. (c) 2012 elsevier b.v. all rights reserved.
学科主题	物理化学
WOS标题词	science & technology ; physical sciences
类目[WOS]	chemistry, physical
研究领域[WOS]	chemistry
关键词[WOS]	free-energy calculations ; binding free-energies ; protein-protein interactions ; particle mesh ewald ; mm-pbsa ; implicit solvent ; p53 restoration ; drug discovery ; wild-type ; cells
收录类别	SCI
语种	英语
WOS记录号	WOS:000302432600006
公开日期	2013-10-11
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/118137]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
作者单位	1.Shandong Jiaotong Univ, Dept Math & Phys, Jinan 250031, Peoples R China 2.Shandong Jiaotong Univ, Dept Foreign Language, Jinan 250031, Peoples R China 3.Chinese Acad Sci, Dalian Inst Chem Phys, State Kay Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116011, Peoples R China
推荐引用方式 GB/T 7714	Cheng, Wei-yuan,Chen, Jian-zhong,Liang, Zhi-qiang,et al. A computational analysis of interaction mechanisms of peptide and non-peptide inhibitors with MDMX based on molecular dynamics simulation[J]. computational and theoretical chemistry,2012,984:43-50.
APA	Cheng, Wei-yuan.,Chen, Jian-zhong.,Liang, Zhi-qiang.,Li, Guo-hui.,Yi, Chang-hong.,...&Wang, Ke-yan.(2012).A computational analysis of interaction mechanisms of peptide and non-peptide inhibitors with MDMX based on molecular dynamics simulation.computational and theoretical chemistry,984,43-50.
MLA	Cheng, Wei-yuan,et al."A computational analysis of interaction mechanisms of peptide and non-peptide inhibitors with MDMX based on molecular dynamics simulation".computational and theoretical chemistry 984(2012):43-50.