A fast mathematical programming procedure for simultaneous fitting of assembly components into cryoEM density maps

doi:10.1093/bioinformatics/btq201

CSpace > 应用数学研究所

	A fast mathematical programming procedure for simultaneous fitting of assembly components into cryoEM density maps
	Zhang, Shihua2,3 ; Vasishtan, Daven 1; Xu, Min 2; Topf, Maya 1; Alber, Frank 2
	2010-06-15
发表期刊	BIOINFORMATICS
ISSN	1367-4803
卷号	26 期号:12 页码:i261-i268
摘要	Motivation: Single-particle cryo electron microscopy (cryoEM) typically produces density maps of macromolecular assemblies at intermediate to low resolution (similar to 5-30 angstrom). By fitting high-resolution structures of assembly components into these maps, pseudoatomic models can be obtained. Optimizing the quality-of-fit of all components simultaneously is challenging due to the large search space that makes the exhaustive search over all possible component configurations computationally unfeasible. Results: We developed an efficient mathematical programming algorithm that simultaneously fits all component structures into an assembly density map. The fitting is formulated as a point set matching problem involving several point sets that represent component and assembly densities at a reduced complexity level. In contrast to other point matching algorithms, our algorithm is able to match multiple point sets simultaneously and not only based on their geometrical equivalence, but also based on the similarity of the density in the immediate point neighborhood. In addition, we present an efficient refinement method based on the Iterative Closest Point registration algorithm. The integer quadratic programming method generates an assembly configuration in a few seconds. This efficiency allows the generation of an ensemble of candidate solutions that can be assessed by an independent scoring function. We benchmarked the method using simulated density maps of 11 protein assemblies at 20 angstrom, and an experimental cryoEM map at 23.5 angstrom resolution. Our method was able to generate assembly structures with root-mean-square errors <6.5 angstrom, which have been further reduced to <1.8 angstrom by the local refinement procedure. Availability: The program is available upon request as a Matlab code package. Contact: alber@usc.edu and m.topf@cryst.bbk.ac.uk Supplementary information: Supplementary data are available at Bioinformatics Online.
DOI	10.1093/bioinformatics/btq201
语种	英语
资助项目	Human Frontier Science Program[RGY0079/2009-C] ; Alfred P. Sloan Research foundation ; BBSRC ; MRC[G0600084] ; Scientific Research Foundation of the Chinese Academy of Sciences ; Pew Charitable Trusts
WOS研究方向	Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Computer Science ; Mathematical & Computational Biology ; Mathematics
WOS类目	Biochemical Research Methods ; Biotechnology & Applied Microbiology ; Computer Science, Interdisciplinary Applications ; Mathematical & Computational Biology ; Statistics & Probability
WOS记录号	WOS:000278689000032
出版者	OXFORD UNIV PRESS
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/9577
专题	应用数学研究所
通讯作者	Topf, Maya
作者单位	1.Univ London, Birkbeck Coll, Inst Struct & Mol Biol, Dept Biol Sci, London, England 2.Univ So Calif, Program Mol & Computat Biol, Los Angeles, CA USA 3.CAS, Acad Math & Syst Sci, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Shihua,Vasishtan, Daven,Xu, Min,et al. A fast mathematical programming procedure for simultaneous fitting of assembly components into cryoEM density maps[J]. BIOINFORMATICS,2010,26(12):i261-i268.
APA	Zhang, Shihua,Vasishtan, Daven,Xu, Min,Topf, Maya,&Alber, Frank.(2010).A fast mathematical programming procedure for simultaneous fitting of assembly components into cryoEM density maps.BIOINFORMATICS,26(12),i261-i268.
MLA	Zhang, Shihua,et al."A fast mathematical programming procedure for simultaneous fitting of assembly components into cryoEM density maps".BIOINFORMATICS 26.12(2010):i261-i268.