DICP OpenIR
Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations
Zhang, Yuxin1,2,3; Huang, Xiaoqin2; Han, Keli1; Zheng, Fang2,3; Zhan, Chang-Guo2,3
KeywordEsterase Cocaine Binding Process Energy Barrier
Source PublicationCHEMICO-BIOLOGICAL INTERACTIONS
2016-11-25
DOI10.1016/j.cbi.2016.05.011
Volume259Pages:142-147
Indexed BySCI ; ISTP
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS KeywordHIGH-ACTIVITY MUTANTS ; BUTYRYLCHOLINESTERASE-CATALYZED HYDROLYSIS ; FUNDAMENTAL REACTION-MECHANISM ; PARTICLE-MESH EWALD ; TRANSITION-STATES ; PERTURBATION SIMULATION ; (-)-COCAINE HYDROLYSIS ; COMPUTATIONAL DESIGN ; REACTION PATHWAY ; HYDROLASE
AbstractThe 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.
Language英语
WOS IDWOS:000388843500014
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/150421
Collection中国科学院大连化学物理研究所
Affiliation1.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
Recommended Citation
GB/T 7714
Zhang, Yuxin,Huang, Xiaoqin,Han, Keli,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 Zhang, Yuxin,Huang, Xiaoqin,Han, Keli,Zheng, Fang,&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 Zhang, Yuxin,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.
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