| Application of a SCC-DFTB QM/MM approach to the investigation of the catalytic mechanism of fatty acid amide hydrolase. | |
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MedLine Citation:
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PMID: 21365225 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Luigi Capoferri; Marco Mor; Jitnapa Sirirak; Ewa Chudyk; Adrian J Mulholland; Alessio Lodola |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-03-02 |
Journal Detail:
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Title: Journal of molecular modeling Volume: 17 ISSN: 0948-5023 ISO Abbreviation: J Mol Model Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-08 Completed Date: 2012-01-20 Revised Date: 2013-03-15 |
Medline Journal Info:
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Nlm Unique ID: 9806569 Medline TA: J Mol Model Country: Germany |
Other Details:
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Languages: eng Pagination: 2375-83 Citation Subset: IM |
Affiliation:
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Dipartimento Farmaceutico, Università degli Studi di Parma, viale G. P. Usberti 27/A Campus Universitario, 43124, Parma, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acylation Amidohydrolases / chemistry* Amino Acid Motifs Biocatalysis Catalytic Domain Models, Chemical Molecular Dynamics Simulation* Quantum Theory Thermodynamics |
| Chemical | |
Reg. No./Substance:
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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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