Exploration of Multi-State Conformational Dynamics and Underlying Global Functional Landscape of Maltose Binding Protein

CORC > 武汉物理与数学研究所 > 中国科学院武汉物理与数学研究所 > 磁共振应用研究部

	Exploration of Multi-State Conformational Dynamics and Underlying Global Functional Landscape of Maltose Binding Protein
	Wang, Yong 1; Tang, Chun 2; Wang, Erkang 1; Wang, Jin 1,3,4
刊名	PLOS COMPUTATIONAL BIOLOGY
	2012-04-01
卷号	8 期号:4
英文摘要	An increasing number of biological machines have been revealed to have more than two macroscopic states. Quantifying the underlying multiple-basin functional landscape is essential for understanding their functions. However, the present models seem to be insufficient to describe such multiple-state systems. To meet this challenge, we have developed a coarse grained triple-basin structure-based model with implicit ligand. Based on our model, the constructed functional landscape is sufficiently sampled by the brute-force molecular dynamics simulation. We explored maltose-binding protein (MBP) which undergoes large-scale domain motion between open, apo-closed (partially closed) and holo-closed (fully closed) states responding to ligand binding. We revealed an underlying mechanism whereby major induced fit and minor population shift pathways co-exist by quantitative flux analysis. We found that the hinge regions play an important role in the functional dynamics as well as that increases in its flexibility promote population shifts. This finding provides a theoretical explanation of the mechanistic discrepancies in PBP protein family. We also found a functional "backtracking" behavior that favors conformational change. We further explored the underlying folding landscape in response to ligand binding. Consistent with earlier experimental findings, the presence of ligand increases the cooperativity and stability of MBP. This work provides the first study to explore the folding dynamics and functional dynamics under the same theoretical framework using our triple-basin functional model.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemical Research Methods ; Mathematical & Computational Biology
研究领域[WOS]	Biochemistry & Molecular Biology ; Mathematical & Computational Biology
关键词[WOS]	INDUCED STRUCTURAL-CHANGES ; UNITED-RESIDUE MODEL ; INDUCED-FIT ; ADENYLATE KINASE ; LIGAND-BINDING ; MOLECULAR-DYNAMICS ; ENERGY LANDSCAPES ; BETA-CYCLODEXTRIN ; ACTIVE-TRANSPORT ; SINGLE-MOLECULE
收录类别	SCI
语种	英语
WOS记录号	WOS:000303440400023
公开日期	2015-07-14
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/1580]
专题	武汉物理与数学研究所_磁共振应用研究部
作者单位	1.Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Changchun 130022, Jilin, Peoples R China 2.Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan, Hubei, Peoples R China 3.Jilin Univ, Coll Phys, Changchun 130023, Jilin, Peoples R China 4.SUNY Stony Brook, Dept Chem Phys & Appl Math, Stony Brook, NY 11794 USA
推荐引用方式 GB/T 7714	Wang, Yong,Tang, Chun,Wang, Erkang,et al. Exploration of Multi-State Conformational Dynamics and Underlying Global Functional Landscape of Maltose Binding Protein[J]. PLOS COMPUTATIONAL BIOLOGY,2012,8(4).
APA	Wang, Yong,Tang, Chun,Wang, Erkang,&Wang, Jin.(2012).Exploration of Multi-State Conformational Dynamics and Underlying Global Functional Landscape of Maltose Binding Protein.PLOS COMPUTATIONAL BIOLOGY,8(4).
MLA	Wang, Yong,et al."Exploration of Multi-State Conformational Dynamics and Underlying Global Functional Landscape of Maltose Binding Protein".PLOS COMPUTATIONAL BIOLOGY 8.4(2012).