Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking

doi:10.1002/prot.21778

	Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking
	Li, Weihua 1; Tang, Yun 1; Liu, Hong2 ; Cheng, Jiagao 1; Zhu, Weiliang2 ; Jiang, Hualiang1,2
刊名	PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
	2008-05-01
卷号	71 期号:2 页码:938-949
关键词	cytochrome P450 2J2 homology modeling molecular dynamics molecular docking
ISSN号	0887-3585
DOI	10.1002/prot.21778
文献子类	Article
英文摘要	Cytochrome P450 (P450) 2J2 catalyzes epoxidation of arachidonic acid to eicosatrienoic acids, which are related to a variety of diseases such as coronary artery disease, hypertension, and carcinogenesis. Recent experimental data also suggest that P450 2J2 could be a novel biomarker and a potential target for cancer therapy. However, the active site topology and substrate specificity of this enzyme remain unclear. In this study, a three-dimensional model of human P450 2J2 was first constructed on the basis of the crystal structure of human P450 2 9 in complex with a substrate using homology modeling method, an refined by molecular dynamics simulation. Flexible docking approaches were then employed to dock four ligands into the active site of P450 2J2 in order to probe the ligand-binding modes. By analyzing the results, active site architecture and certain key residues responsible for substrate specificity were identified on the enzyme, which might be very helpful for understanding the enzyme's biological role and providing insights for designing novel inhibitors of P450 2J2.
WOS关键词	CRYSTAL-STRUCTURE ; ACTIVE-SITE ; SUBSTRATE-SPECIFICITY ; POSSIBLE PATHWAY(S) ; AMINO-ACID ; IN-SILICO ; CYP2J2 ; METABOLISM ; RESOLUTION ; 3A4
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	WILEY-LISS
WOS记录号	WOS:000254263400036
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272934]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室药物发现与设计中心
通讯作者	Tang, Yun
作者单位	1.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Ctr Drug Discovery & Design, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Li, Weihua,Tang, Yun,Liu, Hong,et al. Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking[J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,2008,71(2):938-949.
APA	Li, Weihua,Tang, Yun,Liu, Hong,Cheng, Jiagao,Zhu, Weiliang,&Jiang, Hualiang.(2008).Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking.PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,71(2),938-949.
MLA	Li, Weihua,et al."Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking".PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 71.2(2008):938-949.