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Abstract
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.
Original language | English |
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Pages (from-to) | 2375-2383 |
Number of pages | 9 |
Journal | Journal of Molecular Modeling |
Volume | 17 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 2011 |
Keywords
- QM/MM
- SCC-DFTB
- FAAH
- Reaction mechanism
- Computational enzymology
- FUNCTIONAL TIGHT-BINDING
- QUANTUM-CHEMICAL METHODS
- A BETA-LACTAMASE
- ANTIBIOTIC-RESISTANCE
- COMPUTER-SIMULATIONS
- ENZYME CATALYSIS
- DYNAMICS
- SYSTEMS
- DETERMINANTS
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Dive into the research topics of 'Application of a SCC-DFTB QM/MM approach to the investigation of the catalytic mechanism of fatty acid amide hydrolase'. Together they form a unique fingerprint.Projects
- 1 Finished
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COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE
Mulholland, A. J. (Principal Investigator)
1/10/08 → 1/04/14
Project: Research