Automatch: Target-binding protein design and enzyme design by automatic pinpointing potential active sites in available protein scaffolds

doi:10.1002/prot.24009

CORC > 化学研究所 > 中国科学院化学研究所

	Automatch: Target-binding protein design and enzyme design by automatic pinpointing potential active sites in available protein scaffolds
	Zhang, Changsheng 1; Lai, Luhua 1,2
刊名	PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
	2012-04-01
卷号	80 期号:4 页码:1078-1094
关键词	Active Sites Matching Enzyme Design Target-binding Protein Design Backbone Flexibility Active Site Recapitulation
ISSN号	0887-3585
DOI	10.1002/prot.24009
英文摘要	Proteins perform their functions mainly via active sites, whereas other parts of the proteins comprise the scaffolds, which support the active sites. One strategy for protein functional design is transplanting active sites, such as catalytic sites for enzyme or binding hot spots for proteinprotein interactions, onto a new scaffold. AutoMatch is a new program designed for efficiently elucidating suitable scaffolds and potential sites on the scaffolds. Backrub motions are used to treat backbone flexibility during the design process. A step-by-step checking strategy and cluster-representation examination strategy were developed to solve the large combinatorial problem for the matching of active-site conformations. In addition, a grid-based binding energy scoring method was used to filter the solutions. An enzyme design benchmark and a proteinprotein interaction design benchmark were built to test the algorithm. AutoMatch could identify the hot spots in the nonbinding protein and rank them within the top five results for 8 of 10 target-binding protein design cases. In addition, among the 15 enzymes tested, AutoMatch can identify the catalytic active sites in the apoprotein and rank them within the top five results for 13 cases. AutoMatch was also tested for screening scaffold library in designing binding proteins targeting influenza hemagglutinin, HIV gp120, and epidermal growth factor receptor kinase, respectively. AutoMatch, and the two test sets, ActApo and ActFree, are available for noncommercial applications at . Proteins 2012; (c) 2011 Wiley Periodicals, Inc.
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000300984700009
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/48805]
专题	中国科学院化学研究所
通讯作者	Lai, Luhua
作者单位	1.Peking Univ, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, BNLMS, Beijing 100871, Peoples R China 2.Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Changsheng,Lai, Luhua. Automatch: Target-binding protein design and enzyme design by automatic pinpointing potential active sites in available protein scaffolds[J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,2012,80(4):1078-1094.
APA	Zhang, Changsheng,&Lai, Luhua.(2012).Automatch: Target-binding protein design and enzyme design by automatic pinpointing potential active sites in available protein scaffolds.PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS,80(4),1078-1094.
MLA	Zhang, Changsheng,et al."Automatch: Target-binding protein design and enzyme design by automatic pinpointing potential active sites in available protein scaffolds".PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS 80.4(2012):1078-1094.