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

doi:10.1002/prot.24009

CORC > 北京大学 > 化学与分子工程学院

	Automatch: Target-binding protein design and enzyme design by automatic pinpointing potential active sites in available protein scaffolds
	Zhang, Changsheng ; Lai, Luhua
刊名	proteins structure function and bioinformatics
	2012
关键词	active sites matching enzyme design target-binding protein design backbone flexibility active site recapitulation COMPUTATIONAL DESIGN HOT-SPOTS HIV-1 GP120 MECHANISTIC IMPLICATIONS CRYSTAL-STRUCTURES INTERFACE SUBSTRATE EVOLUTION RECEPTOR DATABASE
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.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000300984700009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemistry & Molecular Biology; Biophysics; SCI(E); PubMed; 16; ARTICLE; 4; 1078-1094; 80
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/149876]
专题	化学与分子工程学院
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.
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.
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 (2012).