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

Yuxin Zhang, Xiaoqin Huang, Keli Han, Fang Zheng, Chang Guo Zhan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 (∼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 ∼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 (∼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.

Original languageEnglish
Pages (from-to)142-147
Number of pages6
JournalChemico-Biological Interactions
Volume259
DOIs
StatePublished - Nov 25 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ireland Ltd

Keywords

  • Binding process
  • Cocaine
  • Energy barrier
  • Esterase

ASJC Scopus subject areas

  • Toxicology

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