A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules

doi:10.1007/s13238-015-0229-2

CORC > 计算技术研究所 > 中国科学院计算技术研究所 > 中国科学院计算技术研究所期刊论文 > 英文

	A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules
	Shan, Hong 2; Wang, Zihao 3,4,5; Zhang, Fa 3,4; Xiong, Yong 6; Yin, Chang-Cheng 2; Sun, Fei 1,5,7
刊名	PROTEIN & CELL
	2016
卷号	7 期号:1 页码:46-62
关键词	cryo-electron microscopy single particle analysis conformational heterogeneity rigid module local optimization refinement
ISSN号	1674-800X
DOI	10.1007/s13238-015-0229-2
英文摘要	Single particle analysis, which can be regarded as an average of signals from thousands or even millions of particle projections, is an efficient method to study the three-dimensional structures of biological macromolecules. An intrinsic assumption in single particle analysis is that all the analyzed particles must have identical composition and conformation. Thus specimen heterogeneity in either composition or conformation has raised great challenges for high-resolution analysis. For particles with multiple conformations, inaccurate alignments and orientation parameters will yield an averaged map with diminished resolution and smeared density. Besides extensive classification approaches, here based on the assumption that the macromolecular complex is made up of multiple rigid modules whose relative orientations and positions are in slight fluctuation around equilibriums, we propose a new method called as local optimization refinement to address this conformational heterogeneity for an improved resolution. The key idea is to optimize the orientation and shift parameters of each rigid module and then reconstruct their three-dimensional structures individually. Using simulated data of 80S/70S ribosomes with relative fluctuations between the large (60S/50S) and the small (40S/30S) subunits, we tested this algorithm and found that the resolutions of both subunits are significantly improved. Our method provides a proof-of-principle solution for high-resolution single particle analysis of macromolecular complexes with dynamic conformations.
资助项目	Strategic Priority Research Program of Chinese Academy of Sciences[XDB08030202] ; National Basic Research Program (973 Program)[2014CB910700] ; National Basic Research Program (973 Program)[2012CB917200] ; National Basic Research Program (973 Program)[2010CB912400] ; National Natural Science Foundation of China[61232001] ; National Natural Science Foundation of China[61202210]
WOS研究方向	Cell Biology
语种	英语
出版者	HIGHER EDUCATION PRESS
WOS记录号	WOS:000368107900007
内容类型	期刊论文
源URL	[http://119.78.100.204/handle/2XEOYT63/8955]
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Yin, Chang-Cheng
作者单位	1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 2.Peking Univ, Hlth Sci Ctr, Coll Basic Med Sci, Dept Biophys, Beijing 100191, Peoples R China 3.Chinese Acad Sci, Inst Comp Technol, Key Lab Intelligent Informat Proc, Beijing 100190, Peoples R China 4.Chinese Acad Sci, Inst Comp Technol, Adv Comp Res Lab, Beijing 100190, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06511 USA 7.Chinese Acad Sci, Inst Biophys, Ctr Biol Imaging, Beijing 100101, Peoples R China
推荐引用方式 GB/T 7714	Shan, Hong,Wang, Zihao,Zhang, Fa,et al. A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules[J]. PROTEIN & CELL,2016,7(1):46-62.
APA	Shan, Hong,Wang, Zihao,Zhang, Fa,Xiong, Yong,Yin, Chang-Cheng,&Sun, Fei.(2016).A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules.PROTEIN & CELL,7(1),46-62.
MLA	Shan, Hong,et al."A local-optimization refinement algorithm in single particle analysis for macromolecular complex with multiple rigid modules".PROTEIN & CELL 7.1(2016):46-62.