Effective Conformational Sampling in Explicit Solvent with Gaussian Biased Accelerated Molecular Dynamics

doi:10.1021/acs.jctc.7b00242

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Effective Conformational Sampling in Explicit Solvent with Gaussian Biased Accelerated Molecular Dynamics
	Shao, Qiang1,2 ; Zhu, Weiliang1,2
刊名	JOURNAL OF CHEMICAL THEORY AND COMPUTATION
	2017-09
卷号	13 期号:9 页码:4240-4252
ISSN号	1549-9618
DOI	10.1021/acs.jctc.7b00242
文献子类	Article
英文摘要	In this Article, a user-friendly Gaussian biased accelerated molecular dynamics (GbAMD) method is presented that uses a sum of Gaussians of potential energies as the biased force to accelerate the conformational sampling. The easy parameter setting of GbAMD is demonstrated in a variety of simulation tests for the conformational transitions of proteins with various complexity including the folding of Trpcage, GB1p, and HP35 peptides as well as the functional conformational changes of nCaM and HIV-1 PR proteins. Additionally, the ability of GbAMD in conformational sampling and free-energy evaluation is quantitatively assessed through the comparison of GbAMD simulations on the folding of a-helical Trpcage and beta-hairpin GB1p with the accompanying standard dual boost AMD and conventional MD (cMD) simulations. While GbAMD can fold both peptides into their native structures repeatedly in individual trajectories, AMD can only fold Trpcage and cMD fails the folding in both cases. As a result, only GbAMD can quantitatively measure the properties of the equilibrium conformational ensemble of protein folding consistent with experimental data. Also notable is that the structural properties of the indispensable unfolded and transition states in the folding pathways of Trpcage and GB1p characterized by GbAMD simulations are in great agreement with previous simulations on the two peptides. In summary, GbAMD has an effective conformational sampling ability that provides a convenient and effective access for simulating the structural dynamics of biomolecular systems.
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 (the second phase)[U1501501]
WOS关键词	PROTEIN-FOLDING SIMULATIONS ; FREE-ENERGY CALCULATION ; TRP-CAGE ; BETA-HAIRPIN ; FORCE-FIELD ; SIDE-CHAIN ; BIOMOLECULAR SIMULATION ; UNFOLDED STATE ; LIQUID WATER ; GB1 HAIRPIN
WOS研究方向	Chemistry ; Physics
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000410867500027
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272495]
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. Effective Conformational Sampling in Explicit Solvent with Gaussian Biased Accelerated Molecular Dynamics[J]. JOURNAL OF CHEMICAL THEORY AND COMPUTATION,2017,13(9):4240-4252.
APA	Shao, Qiang,&Zhu, Weiliang.(2017).Effective Conformational Sampling in Explicit Solvent with Gaussian Biased Accelerated Molecular Dynamics.JOURNAL OF CHEMICAL THEORY AND COMPUTATION,13(9),4240-4252.
MLA	Shao, Qiang,et al."Effective Conformational Sampling in Explicit Solvent with Gaussian Biased Accelerated Molecular Dynamics".JOURNAL OF CHEMICAL THEORY AND COMPUTATION 13.9(2017):4240-4252.