ArticleThe journal of physical chemistry. B2010
Free energy perturbation simulation on transition states and high-activity mutants of human butyrylcholinesterase for (-)-cocaine hydrolysis.
Article in The journal of physical chemistry. B, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase.Scientific reports · 2024Article
- Catalytic activities of a highly efficient cocaine hydrolase for hydrolysis of biologically active cocaine metabolites norcocaine and benzoylecgonine.Scientific reports · 2023Article
- Fast Prediction of Binding Affinities of the SARS-CoV-2 Spike Protein Mutant N501Y (UK Variant) with ACE2 and Miniprotein Drug Candidates.The journal of physical chemistry. B · 2021Article
- Catalytic activities of cocaine hydrolases against the most toxic cocaine metabolite norcocaethylene.Organic & biomolecular chemistry · 2020Article
- Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations.Chemico-biological interactions · 2016Article
- Reaction Pathway for Cocaine Hydrolase-Catalyzed Hydrolysis of (+)-Cocaine.Theoretical chemistry accounts · 2016Article
- Accurate calculation of mutational effects on the thermodynamics of inhibitor binding to p38α MAP kinase: a combined computational and experimental study.Journal of chemical theory and computation · 2013Article
- Catalytic activities of a cocaine hydrolase engineered from human butyrylcholinesterase against (+)- and (-)-cocaine.Chemico-biological interactions · 2013Article
- Computation of relative binding free energy for an inhibitor and its analogs binding with Erk kinase using thermodynamic integration MD simulation.Journal of computer-aided molecular design · 2012Article
- Cocaine esterase-cocaine binding process and the free energy profiles by molecular dynamics and potential of mean force simulations.The journal of physical chemistry. B · 2012Article
- Reaction pathway and free energy profiles for butyrylcholinesterase-catalyzed hydrolysis of acetylthiocholine.Biochemistry · 2012Article
- His-tag truncated butyrylcholinesterase as a useful construct for in vitro characterization of wild-type and variant butyrylcholinesterases.Protein expression and purification · 2011Article
- Reaction pathway and free energy profile for butyrylcholinesterase-catalyzed hydrolysis of acetylcholine.The journal of physical chemistry. B · 2011Article
- Enzyme-therapy approaches for the treatment of drug overdose and addiction.Future medicinal chemistry · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
A unified computational approach based on free energy perturbation (FEP) simulations of transition states has been employed to calculate the mutation-caused shifts of the free energy change from the free enzyme to the rate-determining transition state for (-)-cocaine hydrolysis catalyzed by the currently most promising series of mutants of human butyrylcholinesterase (BChE) that contain the A199S/A328W/Y332G mutations. The FEP simulations were followed by Michaelis-Menten kinetics analysis determining the individual k(cat) and K(M) values missing for the A199S/F227A/A328W/Y332G mutant in this series. The calculated mutation-caused shifts of the free energy change from the free enzyme to the rate-determining transition state are in good agreement with the experimental kinetic data, demonstrating that the unified computational approach based on the FEP simulations of the transition states may be valuable for future computational design of new BChE mutants with a further improved catalytic efficiency against (-)-cocaine.
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