Document Detail


Application of a SCC-DFTB QM/MM approach to the investigation of the catalytic mechanism of fatty acid amide hydrolase.
MedLine Citation:
PMID:  21365225     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Self-consistent charge density functional tight binding (SCC-DFTB) is a promising method for hybrid quantum mechanics/molecular mechanics (QM/MM) simulations of enzyme-catalyzed reactions. The acylation reaction of fatty acid amide hydrolase (FAAH), a promising drug target, was investigated by applying a SCC-DFTB/CHARMM27 scheme. Calculated potential energy barriers resulted in reasonable agreement with experiments for oleamide (OA) and oleoylmethyl ester (OME) substrates, outperforming previous calculations performed at the PM3/CHARMM22 level. Furthermore, the experimental preference of FAAH in hydrolyzing OA faster than OME was adequately reproduced by calculations. All these findings indicate that the SCC-DFTB/CHARMM27 approach can be successfully applied to mechanistic investigations of FAAH-catalyzed reactions.
Authors:
Luigi Capoferri; Marco Mor; Jitnapa Sirirak; Ewa Chudyk; Adrian J Mulholland; Alessio Lodola
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-02
Journal Detail:
Title:  Journal of molecular modeling     Volume:  17     ISSN:  0948-5023     ISO Abbreviation:  J Mol Model     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-08     Completed Date:  2012-01-20     Revised Date:  2013-03-15    
Medline Journal Info:
Nlm Unique ID:  9806569     Medline TA:  J Mol Model     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2375-83     Citation Subset:  IM    
Affiliation:
Dipartimento Farmaceutico, Università degli Studi di Parma, viale G. P. Usberti 27/A Campus Universitario, 43124, Parma, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acylation
Amidohydrolases / chemistry*
Amino Acid Motifs
Biocatalysis
Catalytic Domain
Models, Chemical
Molecular Dynamics Simulation*
Quantum Theory
Thermodynamics
Chemical
Reg. No./Substance:
EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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