Evidence map›Paper›PMID 27163853›Full record

ArticleChemico-biological interactions2016

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

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemico-biological interactions, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yuxin ZhangState Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science, Zhongshan Road 457, Dalian 116023, PR China; Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
Xiaoqin HuangMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
Keli HanState Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science, Zhongshan Road 457, Dalian 116023, PR China.
Fang ZhengMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
Chang-Guo ZhanMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA. Electronic address: zhan@uky.edu.

Funding

Development of Long-acting Cocaine Hydrolase as a Treatment for Cocaine AbuseUH3DA041115 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2017 to 2019
$3.8M
Long-lasting cocaine-metabolizing enzyme for cocaine addiction treatmentR01DA035552 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2013 to 2015
$3.4M
High-activity mutants of cocaine esterase for treatment of drug addictionR01DA025100 · NIDA · UNIVERSITY OF KENTUCKY · PI LANDRY, DONALD W, WOODS, JAMES H · 2008 to 2012
$2.5M
Redesign of Butyrylcholinesterase for Cocaine MetabolismR01DA013930 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2003 to 2010
$2.4M
Development of Long-acting Cocaine Hydrolase as a Treatment for Cocaine AbuseUH2DA041115 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2015 to 2016
$2.2M
Development of a Cocaine-Metabolizing Enzyme for Drug Overdose TreatmentR01DA032910 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2012 to 2015
$1.8M
NIDA NIH HHS R01 DA013930NIDA NIH HHS R01 DA025100NIDA NIH HHS R01 DA032910NIDA NIH HHS R01 DA035552NIDA NIH HHS UH2 DA041115NIDA NIH HHS UH3 DA041115
6 · The paper itself

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 K

Indexed as

Binding SitesCarboxylic Ester HydrolasesCocaineMolecular Dynamics SimulationProtein BindingThermodynamicsCarboxylic Ester HydrolasesCocainecocaine esteraseBinding processCocaineEnergy barrierEsterase

Identifiers

PMID27163853
PMCPMC5097894

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.