Paper Report for: Zhang_2016_Chem.Biol.Interact_259_142
Reference
Title: Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations Zhang Y, Huang X, Han K, Zheng F, Zhan CG Ref: Chemico-Biological Interactions, 259:142, 2016 : PubMed
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 ( approximately 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 approximately 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 ( approximately 0.2 kcal/mol), which is qualitatively consistent with the nearly same experimental KM 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.
        
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Zhang Y, Huang X, Han K, Zheng F, Zhan CG (2016) Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations Chemico-Biological Interactions259: 142-147
Zhang Y, Huang X, Han K, Zheng F, Zhan CG (2016) Chemico-Biological Interactions259: 142-147