Dynamic Mechanism of Fatty Acid Transport across Cellular Membranes through FadL: Molecular Dynamics Simulations

doi:10.1021/jp710964x

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	Dynamic Mechanism of Fatty Acid Transport across Cellular Membranes through FadL: Molecular Dynamics Simulations
	Zou, Hanjun 1,3; Zheng, Mingyue1,3 ; Luo, Xiaomin1,3 ; Zhu, Weiliang1,3 ; Chen, Kaixian1,3 ; Shen, Jianhua1,2,3 ; Jiang, Hualiang1,2,3
刊名	JOURNAL OF PHYSICAL CHEMISTRY B
	2008-10-16
卷号	112 期号:41 页码:13070-13078
ISSN号	1520-6106
DOI	10.1021/jp710964x
文献子类	Article
英文摘要	FadL is an important member of the family of fatty acid transport proteins within membranes. In this study, I I conventional molecular dynamics (CMD) and 25 steered molecular dynamics (SMD) simulations were performed to investigate the dynamic mechanism of transport of long-chain fatty acids (LCFAs) across FadL. The CMD simulations addressed the intrinsically dynamic behavior of FadL. Both the CMD and SMD simulations revealed that a fatty acid molecule can move diffusively to a high-affinity site (HAS) from a low-affinity site (LAS). During this process, the swing motion of the L3 segment and the hydrophobic interaction between the fatty acid and FadL could play important roles. Furthermore, 22 of the SMD simulations revealed that fatty acids can pass through the gap between the hatch domain and the transmembrane domain (TMD) by different pathways. SMD simulations identified nine possible pathways for dodecanoic acid (DA) threading the barrel of FadL. The binding free energy profiles between DA and FadL along the MD trajectories indicate that all of the possible pathways are energetically favorable for the transport of fatty acids; however, one pathway (path VI) might be the most probable pathway for DA transport. The reasonability, and reliability of this study were further demonstrated by correlating the MD simulation results with the available mutagenesis results. On the basis of the simulations, a mechanism for the full-length transport process of DA from the extracellular side to the periplasmic space mediated by FadL is proposed.
资助项目	State Key Program of Basic Research of China[2002CB512802] ; Shanghai Supercomputing Center and Computer Network Information Center[00000000]
WOS关键词	PARTICLE MESH EWALD ; OUTER-MEMBRANE ; ESCHERICHIA-COLI ; PROTEIN FADL ; PORE DIMENSIONS ; OMPF PORIN ; CHANNEL ; BINDING ; FAMILY ; IDENTIFICATION
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000259943200027
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272778]
专题	药物发现与设计中心
通讯作者	Shen, Jianhua
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr,State Key Lab Drug Re, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 3.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Zou, Hanjun,Zheng, Mingyue,Luo, Xiaomin,et al. Dynamic Mechanism of Fatty Acid Transport across Cellular Membranes through FadL: Molecular Dynamics Simulations[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2008,112(41):13070-13078.
APA	Zou, Hanjun.,Zheng, Mingyue.,Luo, Xiaomin.,Zhu, Weiliang.,Chen, Kaixian.,...&Jiang, Hualiang.(2008).Dynamic Mechanism of Fatty Acid Transport across Cellular Membranes through FadL: Molecular Dynamics Simulations.JOURNAL OF PHYSICAL CHEMISTRY B,112(41),13070-13078.
MLA	Zou, Hanjun,et al."Dynamic Mechanism of Fatty Acid Transport across Cellular Membranes through FadL: Molecular Dynamics Simulations".JOURNAL OF PHYSICAL CHEMISTRY B 112.41(2008):13070-13078.