Multi-Scaled Explorations of Binding-Induced Folding of Intrinsically Disordered Protein Inhibitor IA3 to its Target Enzyme

	Multi-Scaled Explorations of Binding-Induced Folding of Intrinsically Disordered Protein Inhibitor IA3 to its Target Enzyme
	Wang J ; Wang Y ; Chu XK ; Hagen SJ ; Han W ; Wang EK
刊名	plos computational biology
	2011
卷号	7 期号:4 页码:1-12
关键词	FLY-CASTING MECHANISM ASPARTIC-PROTEINASE SACCHAROMYCES-CEREVISIAE NONNATIVE INTERACTIONS TOPOLOGICAL FRUSTRATION SECONDARY STRUCTURE MOLECULAR-DYNAMICS RECOGNITION SIMULATIONS KINETICS
ISSN号	1553-734x
通讯作者	wang j
中文摘要	biomolecular function is realized by recognition, and increasing evidence shows that recognition is determined not only by structure but also by flexibility and dynamics. we explored a biomolecular recognition process that involves a major conformational change -protein folding. in particular, we explore the binding-induced folding of ia3, an intrinsically disordered protein that blocks the active site cleft of the yeast aspartic proteinase saccharopepsin (ypra) by folding its own n-terminal residues into an amphipathic alpha helix. we developed a multi-scaled approach that explores the underlying mechanism by combining structure-based molecular dynamics simulations at the residue level with a stochastic path method at the atomic level. both the free energy profile and the associated kinetic paths reveal a common scheme whereby ia3 binds to its target enzyme prior to folding itself into a helix. this theoretical result is consistent with recent time-resolved experiments. furthermore, exploration of the detailed trajectories reveals the important roles of non-native interactions in the initial binding that occurs prior to ia3 folding. in contrast to the common view that non-native interactions contribute only to the roughness of landscapes and impede binding, the non-native interactions here facilitate binding by reducing significantly the entropic search space in the landscape. the information gained from multi-scaled simulations of the folding of this intrinsically disordered protein in the presence of its binding target may prove useful in the design of novel inhibitors of aspartic proteinases.
收录类别	SCI收录期刊论文
语种	英语
WOS记录号	WOS:000289973600002
公开日期	2012-06-11
内容类型	期刊论文
源URL	[http://ir.ciac.jl.cn/handle/322003/44716]
专题	长春应用化学研究所_长春应用化学研究所知识产出_期刊论文
推荐引用方式 GB/T 7714	Wang J,Wang Y,Chu XK,et al. Multi-Scaled Explorations of Binding-Induced Folding of Intrinsically Disordered Protein Inhibitor IA3 to its Target Enzyme[J]. plos computational biology,2011,7(4):1-12.
APA	Wang J,Wang Y,Chu XK,Hagen SJ,Han W,&Wang EK.(2011).Multi-Scaled Explorations of Binding-Induced Folding of Intrinsically Disordered Protein Inhibitor IA3 to its Target Enzyme.plos computational biology,7(4),1-12.
MLA	Wang J,et al."Multi-Scaled Explorations of Binding-Induced Folding of Intrinsically Disordered Protein Inhibitor IA3 to its Target Enzyme".plos computational biology 7.4(2011):1-12.