ProALIGN: Directly Learning Alignments for Protein Structure Prediction via Exploiting Context-Specific Alignment Motifs

doi:10.1089/cmb.2021.0430

	ProALIGN: Directly Learning Alignments for Protein Structure Prediction via Exploiting Context-Specific Alignment Motifs
	Kong, Lupeng 1,2,3; Ju, Fusong 1,2; Zheng, Wei-mou 4; Zhu, Jianwei 5; Sun, Shiwei 1,2; Xu, Jinbo 3; Bu, Dongbo 1,2
	2022-01-21
发表期刊	JOURNAL OF COMPUTATIONAL BIOLOGY
ISSN	1066-5277
页码	14
摘要	Template-based modeling (TBM), including homology modeling and protein threading, is one of the most reliable techniques for protein structure prediction. It predicts protein structure by building an alignment between the query sequence under prediction and the templates with solved structures. However, it is still very challenging to build the optimal sequence-template alignment, especially when only distantly related templates are available. Here we report a novel deep learning approach ProALIGN that can predict much more accurate sequence-template alignment. Like protein sequences consisting of sequence motifs, protein alignments are also composed of frequently occurring alignment motifs with characteristic patterns. Alignment motifs are context-specific as their characteristic patterns are tightly related to sequence contexts of the aligned regions. Inspired by this observation, we represent a protein alignment as a binary matrix (in which 1 denotes an aligned residue pair) and then use a deep convolutional neural network to predict the optimal alignment from the query protein and its template. The trained neural network implicitly but effectively encodes an alignment scoring function, which reduces inaccuracies in the handcrafted scoring functions widely used by the current threading approaches. For a query protein and a template, we apply the neural network to directly infer likelihoods of all possible residue pairs in their entirety, which could effectively consider the correlations among multiple residues. We further construct the alignment with maximum likelihood, and finally build a structure model according to the alignment. Tested on three independent data sets with a total of 6688 protein alignment targets and 80 CASP13 TBM targets, our method achieved much better alignments and 3D structure models than the existing methods, including HHpred, CNFpred, CEthreader, and DeepThreader. These results clearly demonstrate the effectiveness of exploiting the context-specific alignment motifs by deep learning for protein threading.
关键词	deep learning and protein threading protein alignment protein structure prediction
DOI	10.1089/cmb.2021.0430
收录类别	SCI
语种	英语
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:000756282100001
出版者	MARY ANN LIEBERT, INC
引用统计	被引频次：4[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/18991
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Xu, Jinbo; Bu, Dongbo
作者单位	1.Chinese Acad Sci, Inst Comp Technol, Key Lab Intelligent Informat Proc, Beijing, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Toyota Technol Inst, Chicago, IL 60637 USA 4.Chinese Acad Sci, Inst Theoret Phys, Beijing, Peoples R China 5.Microsoft Res Asia, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Kong, Lupeng,Ju, Fusong,Zheng, Wei-mou,et al. ProALIGN: Directly Learning Alignments for Protein Structure Prediction via Exploiting Context-Specific Alignment Motifs[J]. JOURNAL OF COMPUTATIONAL BIOLOGY,2022:14.
APA	Kong, Lupeng.,Ju, Fusong.,Zheng, Wei-mou.,Zhu, Jianwei.,Sun, Shiwei.,...&Bu, Dongbo.(2022).ProALIGN: Directly Learning Alignments for Protein Structure Prediction via Exploiting Context-Specific Alignment Motifs.JOURNAL OF COMPUTATIONAL BIOLOGY,14.
MLA	Kong, Lupeng,et al."ProALIGN: Directly Learning Alignments for Protein Structure Prediction via Exploiting Context-Specific Alignment Motifs".JOURNAL OF COMPUTATIONAL BIOLOGY (2022):14.