Assessing AMBER force fields for protein folding in an implicit solvent

doi:10.1039/c7cp08010g

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	Assessing AMBER force fields for protein folding in an implicit solvent
	Shao, Oiang; Zhu, Weiliang
刊名	PHYSICAL CHEMISTRY CHEMICAL PHYSICS
	2018-03-14
卷号	20 期号:10 页码:7206-7216
ISSN号	1463-9076
DOI	10.1039/c7cp08010g
文献子类	Article
英文摘要	Molecular dynamics (MD) simulation implemented with a state-of-the-art protein force field and implicit solvent model is an attractive approach to investigate protein folding, one of the most perplexing problems in molecular biology. But how well can force fields developed independently of implicit solvent models work together in reproducing diverse protein native structures and measuring the corresponding folding thermodynamics is not always clear. In this work, we performed enhanced sampling MD simulations to assess the ability of six AMBER force fields (FF99SBiIdn, FF99SBnmr, FF12SB, FF14ipq, FF14SB, and FF14SBonlysc) as coupled with a recently improved pair-wise GB-Neck2 model in modeling the folding of two helical and two 1-sheet peptides. Whilst most of the tested force fields can yield roughly similar features for equilibrium conformational ensembles and detailed folding free-energy profiles for short a-helical TC10b in an implicit solvent, the measured counterparts are significantly discrepant in the cases of larger or beta-structured peptides (HP35, 1E0Q, and GTT). Additionally, the calculated folding/unfolding thermodynamic quantities can only partially match the experimental data. Although a combination of the force fields and GB-Neck2 implicit model able to describe all aspects of the folding transitions towards the native structures of all the considered peptides was not identified, we found that FF14SBonlysc coupled with the GB-Neck2 model seems to be a reasonably balanced combination to predict peptide folding preferences.
资助项目	National Key Research and Development Program[2016YFA0502301] ; National Basic Research Program[2014CB910400] ; Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund[U1501501]
WOS关键词	FREE-ENERGY LANDSCAPE ; VILLIN HEADPIECE SUBDOMAIN ; GENERALIZED BORN MODEL ; BETA-HAIRPIN ; EXPLICIT SOLVENT ; SECONDARY STRUCTURE ; SIDE-CHAIN ; SOLVATION MODELS ; WW DOMAIN ; CONFORMATIONAL TRANSITIONS
WOS研究方向	Chemistry ; Physics
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000429286100047
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279853]
专题	药物发现与设计中心
通讯作者	Shao, Oiang
作者单位	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, Oiang,Zhu, Weiliang. Assessing AMBER force fields for protein folding in an implicit solvent[J]. PHYSICAL CHEMISTRY CHEMICAL PHYSICS,2018,20(10):7206-7216.
APA	Shao, Oiang,&Zhu, Weiliang.(2018).Assessing AMBER force fields for protein folding in an implicit solvent.PHYSICAL CHEMISTRY CHEMICAL PHYSICS,20(10),7206-7216.
MLA	Shao, Oiang,et al."Assessing AMBER force fields for protein folding in an implicit solvent".PHYSICAL CHEMISTRY CHEMICAL PHYSICS 20.10(2018):7206-7216.