Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis

doi:10.1038/srep36900

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis
	Chen, Jianzhong 1; Wang, Jinan 2; Zhu, Weiliang2
刊名	SCIENTIFIC REPORTS
	2016-11-10
卷号	6
ISSN号	2045-2322
DOI	10.1038/srep36900
文献子类	Article
英文摘要	More and more researchers are interested in and focused on how a limited repertoire of antibodies can bind and correspondingly protect against an almost limitless diversity of invading antigens. In this work, a series of 200-ns molecular dynamics (MD) simulations followed by principal component (PC) analysis and free energy calculations were performed to probe potential mechanism of conformational diversity of antibody SPE7. The results show that the motion direction of loops H3 and L3 is different relative to each other, implying that a big structural difference exists between these two loops. The calculated energy landscapes suggest that the changes in the backbone angles. and. of H-Y101 and H-Y105 provide significant contributions to the conformational diversity of SPE7. The dihedral angle analyses based on MD trajectories show that the side-chain conformational changes of several key residues H-W33, H-Y105, L-Y34 and L-W93 around binding site of SPE7 play a key role in the conformational diversity of SPE7, which gives a reasonable explanation for potential mechanism of cross-reactivity of single antibody toward multiple antigens.
资助项目	National Natural Science Foundation of China[11274206] ; National Natural Science Foundation of China[81273435] ; National Natural Science Foundation of China[11504206] ; National Natural Science Foundation of China[21403283] ; Shandong province university science and technology project[J14LJ07] ; major development projects of Shandong Jiaotong University[00000000] ; Postdoctoral Science Foundation of China[2014M560362] ; Postdoctoral Science Foundation of China[2015T80467] ; Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund[00000000]
WOS关键词	HIV-1 MONOCLONAL-ANTIBODY ; INDUCED FIT ; CROSS-REACTIVITY ; STRUCTURAL BASIS ; MUTATIONS V32I ; BETA OLIGOMERS ; BINDING MODES ; FORCE-FIELD ; INHIBITORS ; SPECIFICITY
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000387874700001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275815]
专题	药物发现与设计中心
通讯作者	Chen, Jianzhong; Wang, Jinan
作者单位	1.Shandong Jiaotong Univ, Sch Sci, Jinan 250014, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Jianzhong,Wang, Jinan,Zhu, Weiliang. Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis[J]. SCIENTIFIC REPORTS,2016,6.
APA	Chen, Jianzhong,Wang, Jinan,&Zhu, Weiliang.(2016).Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis.SCIENTIFIC REPORTS,6.
MLA	Chen, Jianzhong,et al."Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis".SCIENTIFIC REPORTS 6(2016).