Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations

	Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations
	Zheng, Fang 2,3; Zhang, Yuxin 1,2,3; Huang, Xiaoqin 2; Han, Keli 1; Zhan, Chang-Guo 2,3
刊名	CHEMICO-BIOLOGICAL INTERACTIONS
	2016-11-25
卷号	259 页码:142-147
关键词	Esterase Cocaine Binding process Energy barrier
英文摘要	The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profile of the CocE)-(+)-cocaine binding process in comparison with that of the corresponding CocE-(-)-cocaine binding process. According to the MD simulations, the equilibrium CocE-(+)-cocaine binding mode is similar to the CocE-(-)-cocaine binding mode. However, based on the simulated free energy profiles, a significant free energy barrier (similar to 5 kcal/mol) exists in the CocE-(+)-cocaine binding process whereas no obvious free energy barrier exists in the CocE-(-)-cocaine binding process, although the free energy barrier of similar to 5 kcal/mol is not high enough to really slow down the CocE-(+)-cocaine binding process. In addition, the obtained free energy profiles also demonstrate that (+)-cocaine and (-)-cocaine have very close binding free energies with CocE, with a negligible difference (similar to 0.2 kcal/mol), which is qualitatively consistent with the nearly same experimental K-M values of the CocE enzyme for (+)-cocaine and (-)-cocaine. The consistency between the computational results and available experimental data suggests that the mechanistic insights obtained from this study are reasonable. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
关键词[WOS]	HIGH-ACTIVITY MUTANTS ; BUTYRYLCHOLINESTERASE-CATALYZED HYDROLYSIS ; FUNDAMENTAL REACTION-MECHANISM ; PARTICLE-MESH EWALD ; TRANSITION-STATES ; PERTURBATION SIMULATION ; (-)-COCAINE HYDROLYSIS ; COMPUTATIONAL DESIGN ; REACTION PATHWAY ; HYDROLASE
收录类别	SCI ; ISTP
语种	英语
WOS记录号	WOS:000388843500014
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/150421]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
作者单位	1.Chinese Acad Sci, State Key Lab Mol React Dynam, Dalian Inst Chem Phys, Zhongshan Rd 457, Dalian 116023, Peoples R China 2.Univ Kentucky, Coll Pharm, Mol Modeling & Biopharmaceut Ctr, 789 South Limestone St, Lexington, KY 40536 USA 3.Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, 789 South Limestone St, Lexington, KY 40536 USA
推荐引用方式 GB/T 7714	Zheng, Fang,Zhang, Yuxin,Huang, Xiaoqin,et al. Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2016,259:142-147.
APA	Zheng, Fang,Zhang, Yuxin,Huang, Xiaoqin,Han, Keli,&Zhan, Chang-Guo.(2016).Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations.CHEMICO-BIOLOGICAL INTERACTIONS,259,142-147.
MLA	Zheng, Fang,et al."Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations".CHEMICO-BIOLOGICAL INTERACTIONS 259(2016):142-147.