Molecular insight into the interaction between IFABP and PA by using MM-PBSA and alanine scanning methods

doi:10.1021/jp0713763

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 insight into the interaction between IFABP and PA by using MM-PBSA and alanine scanning methods
	Zou, Hanjun ; Luo, Cheng; Zheng, Suxin ; Luo, Xiaomin; Zhu, Weiliang; Chen, Kaixian; Shen, Jianhua; Jiang, Hualiang
刊名	JOURNAL OF PHYSICAL CHEMISTRY B
	2007-08-02
卷号	111 期号:30 页码:9104-9113
ISSN号	1520-6106
DOI	10.1021/jp0713763
文献子类	Article
英文摘要	The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method combined with alanine-scanning mutagenesis is a very important tool for rational drug design. In this study, molecular dynamics (MD) and MM-PBSA were applied to calculate the binding free energy between the rat intestinal fatty acid binding protein (IFABP) and palmitic acid (PA) to gain insight to the interaction details. Equally spaced snapshots along the trajectory were chosen to perform the binding free energy calculation, which yields a result highly consistent with experimental value with a deviation of 0.4 kcal/mol. Computational alanine scanning was performed on the same set of snapshots by mutating the residues in IFABP to alanine and recomputing the Delta Delta G(binding). By postprocessing a single trajectory of the wild-type complex, the average unsigned error of our calculated Delta Delta G(binding) is below 1.5 kcal/mol for most of the alanine mutations of the noncharged residues (67% in total). To further investigate some particular mutants, three additional dynamical simulations of IFABP Arg126Ala, Arg106Ala, and Arg106Gln mutants were conducted. Recalculated binding free energies are well consistent with the experimental data. Moreover, the ambiguous role of Arg106 caused by the free energy change of the opposite sign when it is mutated to alanine and glutamine respectively is clarified both structurally and energetically. Typically, this can be attributed to the partial electrostatic compensation mainly from Arg56 and the obvious entropy gain in Arg106Ala mutant while not in Arg106Gln mutant. The presented structural model of IFABP-PA complex could be used to guide future studies.
WOS关键词	FATTY-ACID-BINDING ; FREE-ENERGY CALCULATIONS ; ESCHERICHIA-COLI ; DYNAMICS SIMULATIONS ; PROTEIN INTERACTIONS ; CONTINUUM SOLVENT ; BOUND PALMITATE ; LIGAND-BINDING ; WATER ; THERMODYNAMICS
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000248315700058
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273179]
专题	药物发现与设计中心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
通讯作者	Shen, Jianhua
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Zou, Hanjun,Luo, Cheng,Zheng, Suxin,et al. Molecular insight into the interaction between IFABP and PA by using MM-PBSA and alanine scanning methods[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2007,111(30):9104-9113.
APA	Zou, Hanjun.,Luo, Cheng.,Zheng, Suxin.,Luo, Xiaomin.,Zhu, Weiliang.,...&Jiang, Hualiang.(2007).Molecular insight into the interaction between IFABP and PA by using MM-PBSA and alanine scanning methods.JOURNAL OF PHYSICAL CHEMISTRY B,111(30),9104-9113.
MLA	Zou, Hanjun,et al."Molecular insight into the interaction between IFABP and PA by using MM-PBSA and alanine scanning methods".JOURNAL OF PHYSICAL CHEMISTRY B 111.30(2007):9104-9113.