Selective enhanced sampling in dihedral energy facilitates overcoming the dihedral energy increase in protein folding and accelerates the searching for protein native structure

doi:10.1039/c9cp00615j

	Selective enhanced sampling in dihedral energy facilitates overcoming the dihedral energy increase in protein folding and accelerates the searching for protein native structure
	Shao, Qiang 1,2; Yang, Lijiang 2,3,4; Zhu, Weiliang 1,5
刊名	PHYSICAL CHEMISTRY CHEMICAL PHYSICS
	2019-05-28
卷号	21 期号:20 页码:10423-10435
ISSN号	1463-9076
DOI	10.1039/c9cp00615j
通讯作者	Shao, Qiang(qshao@simm.ac.cn) ; Yang, Lijiang(lijiangy@pku.edu.cn)
英文摘要	The dihedral energy function is the most influential parameter in molecular mechanics (MM) force field parameter optimization. A selective enhanced sampling of dihedral energy could effectively reflect the influence of dihedral energy settings on protein secondary structure representation, which in turn testifies the availability of the force field in folding simulation. Here, a Dihedral-based Selective Integrated-Tempering-Sampling Molecular Dynamics (D-SITSMD) simulation method is shown to provide a selective enhanced sampling of dihedral energy without introducing large energetic noise. Its capabilities of searching for protein natively folded structure and providing the underlying folding pathway are evaluated through the folding tests of three peptides (chignolin, TC5b, and HP35) with multiple AMBER force fields (FF14SBonlysc, FF99SBildn, or FF03) and the comparison to presented experimental data and REMD simulations. Both above-mentioned capabilities are improved, displaying the potential of D-SITSMD in the studies of in silico protein folding and structure refinement. Additionally, it is commonly observed among the test simulation systems that their folding processes are thermodynamically favorable for non-bonded vdW and electrostatic energies but unfavorable for dihedral energy, such that the folding barrier height correlated with the dihedral energy increase from the unfolded to folded state whereas the unfolding free energy barrier correlated with the combined increase of vdW and electrostatic energies in the unfolding process. It is speculated that the influence of a force field on the folding barrier of a protein is fulfilled mainly through regulating the contribution of dihedral energy to determine the secondary structure formation in the global folding process.
资助项目	National Key Research and Development Program[2016YFA0502301] ; Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the second phase)[U1501501]
WOS关键词	MOLECULAR-DYNAMICS SIMULATIONS ; VILLIN HEADPIECE SUBDOMAIN ; AMBER FORCE-FIELDS ; SIDE-CHAIN ; BIOMOLECULAR SIMULATION ; EXPLICIT-SOLVENT ; MONTE-CARLO ; THERMODYNAMICS ; PARAMETERS ; ACCURACY
WOS研究方向	Chemistry ; Physics
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000476561000017
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289188]
专题	中国科学院上海药物研究所
通讯作者	Shao, Qiang; Yang, Lijiang
作者单位	1.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Beijing Natl Lab Mol Sci, 1st North St, Beijing 100080, Peoples R China 3.Peking Univ, Inst Theoret & Computat Chem, Coll Chem & Mol Engn, Beijing 100871, Peoples R China 4.Peking Univ, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China 5.Pilot Natl Lab Marine Sci & Technol, Open Studio Druggabil Res Marine Nat Prod, 1 Wenhai Rd, Qingdao 266237, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Shao, Qiang,Yang, Lijiang,Zhu, Weiliang. Selective enhanced sampling in dihedral energy facilitates overcoming the dihedral energy increase in protein folding and accelerates the searching for protein native structure[J]. PHYSICAL CHEMISTRY CHEMICAL PHYSICS,2019,21(20):10423-10435.
APA	Shao, Qiang,Yang, Lijiang,&Zhu, Weiliang.(2019).Selective enhanced sampling in dihedral energy facilitates overcoming the dihedral energy increase in protein folding and accelerates the searching for protein native structure.PHYSICAL CHEMISTRY CHEMICAL PHYSICS,21(20),10423-10435.
MLA	Shao, Qiang,et al."Selective enhanced sampling in dihedral energy facilitates overcoming the dihedral energy increase in protein folding and accelerates the searching for protein native structure".PHYSICAL CHEMISTRY CHEMICAL PHYSICS 21.20(2019):10423-10435.