The Observation of Ligand-Binding-Relevant Open States of Fatty Acid Binding Protein by Molecular Dynamics Simulations and a Markov State Model

doi:10.3390/ijms20143476

	The Observation of Ligand-Binding-Relevant Open States of Fatty Acid Binding Protein by Molecular Dynamics Simulations and a Markov State Model
	Guo, Yue 2,3; Duan, Mojie 2,3; Yang, Minghui 1,2,3
刊名	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
	2019-07-02
卷号	20 期号:14 页码:13
关键词	fatty acid binding protein invisible intermediate states transition time binding mechanism molecular dynamics simulation
ISSN号	1661-6596
DOI	10.3390/ijms20143476
英文摘要	As a member of the fatty acids transporter family, the heart fatty acid binding proteins (HFABPs) are responsible for many important biological activities. The binding mechanism of fatty acid with FABP is critical to the understanding of FABP functions. The uncovering of binding-relevant intermediate states and interactions would greatly increase our knowledge of the binding process. In this work, all-atom molecular dynamics (MD) simulations were performed to characterize the structural properties of nativelike intermediate states. Based on multiple 6 mu s MD simulations and Markov state model (MSM) analysis, several "open" intermediate states were observed. The transition rates between these states and the native closed state are in good agreement with the experimental measurements, which indicates that these intermediate states are binding relevant. As a common property in the open states, the partially unfolded alpha 2 helix generates a larger portal and provides the driving force to facilitate ligand binding. On the other side, there are two kinds of open states for the ligand-binding HFABP: one has the partially unfolded alpha 2 helix, and the other has the looser p-barrel with disjointing beta D-beta E strands. Our results provide atomic-level descriptions of the binding-relevant intermediate states and could improve our understanding of the binding mechanism.
资助项目	National Natural Science Foundation of China[21773298] ; National Natural Science Foundation of China[21773297]
WOS关键词	ESCHERICHIA-COLI ; HOLO FORMS ; APO ; MECHANISMS ; ENTRY ; AMBER
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000480449300100
资助机构	National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/14768]
专题	中国科学院武汉物理与数学研究所
通讯作者	Duan, Mojie; Yang, Minghui
作者单位	1.Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Wuhan 430074, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan Inst Phys & Math,Natl Ctr Magnet Resonance, Wuhan 430071, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Guo, Yue,Duan, Mojie,Yang, Minghui. The Observation of Ligand-Binding-Relevant Open States of Fatty Acid Binding Protein by Molecular Dynamics Simulations and a Markov State Model[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2019,20(14):13.
APA	Guo, Yue,Duan, Mojie,&Yang, Minghui.(2019).The Observation of Ligand-Binding-Relevant Open States of Fatty Acid Binding Protein by Molecular Dynamics Simulations and a Markov State Model.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,20(14),13.
MLA	Guo, Yue,et al."The Observation of Ligand-Binding-Relevant Open States of Fatty Acid Binding Protein by Molecular Dynamics Simulations and a Markov State Model".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 20.14(2019):13.