Binding Modes of Three Inhibitors 8CA, F8A and I4A to A-FABP Studied Based on Molecular Dynamics Simulation

doi:10.1371/journal.pone.0099862

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	Binding Modes of Three Inhibitors 8CA, F8A and I4A to A-FABP Studied Based on Molecular Dynamics Simulation
	Chen, Jianzhong 2; Wang, Jinan 1; Zhu, Weiliang1
刊名	PLOS ONE
	2014-06-11
卷号	9 期号:6
ISSN号	1932-6203
DOI	10.1371/journal.pone.0099862
文献子类	Article
英文摘要	Adipocyte fatty-acid binding protein (A-FABP) is an important target of drug designs treating some diseases related to lipid-mediated biology. Molecular dynamics (MD) simulations coupled with solvated interaction energy method (SIE) were carried out to study the binding modes of three inhibitors 8CA, F8A and I4A to A-FABP. The rank of our predicted binding affinities is in accordance with experimental data. The results show that the substitution in the position 5 of N-benzyl and the seven-membered ring of N-benzyl-indole carboxylic acids strengthen the I4A binding, while the substitution in the position 2 of N-benzyl weakens the F8A binding. Computational alanine scanning and dynamics analyses were performed and the results suggest that the polar interactions of the positively charged residue R126 with the three inhibitors provide a significant contribution to inhibitor bindings. This polar interaction induces the disappearance of the correlated motion of the C terminus of A-FABP relative to the N terminus and favors the stability of the binding complex. This study is helpful for the rational design of potent inhibitors within the fields of metabolic disease, inflammation and atherosclerosis.
资助项目	National Natural Science Foundation of China[11104164] ; National Natural Science Foundation of China[11274206] ; National Natural Science Foundation of China[31200545] ; National 863 Program[2012AA01A305] ; Dr. Start-up Foundation of Shandong Jiaotong University[00000000] ; Natural Science Foundation of Shandong Jiaotong University[00000000]
WOS关键词	PROTEIN-PROTEIN INTERACTIONS ; SOLVATED INTERACTION ENERGY ; BOUNDARY-ELEMENT METHOD ; PARTICLE MESH EWALD ; COMPUTATIONAL ANALYSIS ; INSULIN-RESISTANCE ; PK(A) VALUES ; FORCE-FIELD ; MM-PBSA ; AP2
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000338631000122
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277027]
专题	药物发现与设计中心
通讯作者	Chen, Jianzhong
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Discovery & Design Ctr, Shanghai, Peoples R China 2.Shandong Jiaotong Univ, Sch Sci, Jinan, Peoples R China;
推荐引用方式 GB/T 7714	Chen, Jianzhong,Wang, Jinan,Zhu, Weiliang. Binding Modes of Three Inhibitors 8CA, F8A and I4A to A-FABP Studied Based on Molecular Dynamics Simulation[J]. PLOS ONE,2014,9(6).
APA	Chen, Jianzhong,Wang, Jinan,&Zhu, Weiliang.(2014).Binding Modes of Three Inhibitors 8CA, F8A and I4A to A-FABP Studied Based on Molecular Dynamics Simulation.PLOS ONE,9(6).
MLA	Chen, Jianzhong,et al."Binding Modes of Three Inhibitors 8CA, F8A and I4A to A-FABP Studied Based on Molecular Dynamics Simulation".PLOS ONE 9.6(2014).