Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants.

Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants. Abstract Text:

Adel Hamza,Hoon Cho,Hsin-Hsiung Tai,Chang-Guo Zhan,

Molecular dynamics (MD) simulations were carried out to study cocaine binding with wild-type human butyrylcholinesterase (BChE) and its mutants based on a recently reported X-ray crystal structure of human BChE. For each BChE-cocaine system, we simulated both the nonprereactive and prereactive complexes in water. Despite the significant difference found at the acyl binding pocket, the simulated structures confirm the fundamental structural and mechanistic insights obtained from earlier computational studies of wild-type BChE with cocaine based on a homology model, e.g. the rate-determining step for BChE-catalyzed hydrolysis of biologically active (-)-cocaine is the (-)-cocaine rotation in the active site from the nonprereactive BChE-(-)-cocaine complex to the prereactive complex. It has been demonstrated that the MD simulations on both the nonprereactive and prereactive BChE-cocaine complexes can clearly reveal whether specific mutations produce the desired BChE-(-)-cocaine binding structures in which the (-)-cocaine rotation is less hindered while the required prereactive BChE-(-)-cocaine binding is maintained. Based on the MD simulations, both A328W/Y332A and A328W/Y332G BChE's are expected to have catalytic activity for (-)-cocaine hydrolysis higher than that of wild-type BChE and the activity of A328W/Y332G BChE should be slightly higher than that of A328W/Y332A BChE due to the less-hindered (-)-cocaine rotation in the mutant BChE's. However, the less-hindered (-)-cocaine rotation is only a necessary condition for a higher activity mutant BChE. The (-)-cocaine rotation is also less hindered in A328W/Y332A/Y419S BChE, but (-)-cocaine binds with A328W/Y332A/Y419S BChE in a way that is not suitable for the catalysis. Thus, A328W/Y332A/Y419S BChE is expected to lose the catalytic activity. The computational predictions were confirmed by our experimental kinetic data, demonstrating that the MD simulation-based computational protocol used in this study is reliable in prediction of the catalytic activity of BChE mutants for (-)-cocaine hydrolysis.

Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants. Publishing Authors By Initials

A Hamza,H Cho,HH Tai,CG Zhan,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The journal of physical chemistry. B

VOLUME: 109

Page Numbers: 4776-82

Journal Abbreviation:

ISSN: 1520-6106

DAY: 17

MONTH: Mar

YEAR: 2005

Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101157530

Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants.

AFFILIATION: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Phys Chem B

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants Related Publications

• Formation of supramolecular permethrin/beta-cyclodextrin nanorods.
• Modeling effects of oxyanion hole on the ester hydrolysis catalyzed by human cholinesterases.
• Modeling subtype-selective agonists binding with alpha4beta2 and alpha7 nicotinic acetylcholine receptors: effects of local binding and long-range electrostatic interactions.
• Molecular dynamics simulation of cocaine binding with human butyrylcholinesterase and its mutants.
• Tyrosine phosphorylation of missing in metastasis protein is implicated in platelet-derived growth factor-mediated cell shape changes.
• [Analysis of anti-ultraviolet characteristic of liquid-crystal display]
• [Analysis of related factors of nasosinusitis after radiotherapy for nasopharyngeal carcinoma]
• [Analysis of the status of diagnosis of acute pulmonary embolism and a study of further strategy to improve the diagnostic level]
• [Antigencity identification of recombinant hepatitis E virus ORF2 protein expressed in Pichia pastoris]
• [Clinicopathologic features of the patients with node-negative metastasis gastric adenocarcinoma and their survival analysis]
• [Composition and structure evolution of carbon nanotube/silica xerogel composites during the process of laser irradiation]
• [Core protein of hepatitis C virus expressed in transgenic mice is associated with the expression of Fas molecule]
• [Determination of 14 trace elements in soybean and its products by atomic absorption spectrometry]
• [Developments of research on "qiu shi" (autumn stone)]
• [Dynamic changes of serum antibody titer and liver ultrastructural pathology in acute sporadic hepatitis E virus infected patients]
• [Effect of huperzine A on cerebral cholinesterase and acetylcholine in elderly patients during recovery from general anesthesia]
• [Electrical conductivity as an indicator of hydrological characteristics in catchment scale]
• [Fluorimetric determination of trace ruthenium in anode slime of alkali chloride factory with 1,10-phenanthroline]
• [Frequency stabilization of diode laser using zeeman spectra]
• [Influence of matrix on the optical limiting effect of metallophthalocyanine doped composite]
• [Karyotype analysis of Echinocodon lobophyllus]
• [Morphological and histological studies of Herba Sedum aizoon]
• [Sequences of 5S-rRNA gene spacer region and comparison of alkaloid content in Fritillaria thunbergii from different habitats]
• [Studies on determination of p-aminophenol and its related compounds prepared with catalytic hydrogenation by reversed-phase high performance liquid chromatography]
• [Study on molecular epidemiology of Borna disease virus in Ningxia and vicinal regions]
• [Study on the relative risk factors of adult measles in a case-control study in Qingdao city]
• [Study on the spectral properties of gallium-phthalocyanine-chloride doped composite gel glass]
• [Study on the structure and optical limiting properties of lead(II) tetrakis (4-cumylphenoxy)-phthalocyanine doped silica gel glass composites]
• [Systematic review of directly observed therapy on tuberculosis control in China]
• [The identification of hippocampus by HPCE]