How Well Can Implicit Solvent Simulations Explore Folding Pathways? A Quantitative Analysis of alpha-Helix Bundle Proteins

doi:10.1021/acs.jctc.7b00726

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	How Well Can Implicit Solvent Simulations Explore Folding Pathways? A Quantitative Analysis of alpha-Helix Bundle Proteins
	Shao, Qiang1,2 ; Zhu, Weiliang1,2
刊名	JOURNAL OF CHEMICAL THEORY AND COMPUTATION
	2017-12
卷号	13 期号:12 页码:6177-6190
ISSN号	1549-9618
DOI	10.1021/acs.jctc.7b00726
文献子类	Article
英文摘要	Protein folding has been posing challenges for molecular simulation for decades. Implicit solvent models are sought as routes to increase the capability of simulation, with trade-offs between computational speed and accuracy. Here, we systematically investigate the folding of a variety of alpha-helix bundle proteins ranging in size from 46 to 102 amino acids using a state-of-the-art force field and an implicit solvent model. The accurate all-atom simulated folding is enabled for six proteins, including for the first time a successful folding of protein with >100 amino acids in implicit solvent. The detailed free-energy landscape analysis sheds light on a set of general principles underlying the folding of alpha-helix bundle proteins, suggesting a hybrid framework/nucleation-condensation mechanism favorably adopted in implicit solvent condition. The similarities and discrepancies of the folding pathways measured among the present implicit solvent simulations and previously reported experiments and explicit solvent simulations are deeply analyzed, providing quantitative assessment for the availability and limitation of implicit solvent simulation in exploring the folding transition of large-size proteins.
资助项目	National Natural Science Foundation of China[21373258] ; National Basic Research Program[2014CB910400] ; Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund[U1501501]
WOS关键词	SINGLE-MOLECULE FRET ; AMBER FORCE-FIELDS ; NUCLEATION-CONDENSATION MECHANISM ; DIFFUSION-COLLISION MODEL ; REDUCED RIBONUCLEASE-A ; FREE-ENERGY LANDSCAPE ; EXPLICIT SOLVENT ; DENATURED STATE ; BETA-HAIRPIN ; SECONDARY STRUCTURE
WOS研究方向	Chemistry ; Physics
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000418205100032
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272366]
专题	药物发现与设计中心
通讯作者	Shao, Qiang
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Shao, Qiang,Zhu, Weiliang. How Well Can Implicit Solvent Simulations Explore Folding Pathways? A Quantitative Analysis of alpha-Helix Bundle Proteins[J]. JOURNAL OF CHEMICAL THEORY AND COMPUTATION,2017,13(12):6177-6190.
APA	Shao, Qiang,&Zhu, Weiliang.(2017).How Well Can Implicit Solvent Simulations Explore Folding Pathways? A Quantitative Analysis of alpha-Helix Bundle Proteins.JOURNAL OF CHEMICAL THEORY AND COMPUTATION,13(12),6177-6190.
MLA	Shao, Qiang,et al."How Well Can Implicit Solvent Simulations Explore Folding Pathways? A Quantitative Analysis of alpha-Helix Bundle Proteins".JOURNAL OF CHEMICAL THEORY AND COMPUTATION 13.12(2017):6177-6190.