Abstract
Since the three-dimensional molecular structure of the benzodiazepine receptors is not yet univoquely known, the direct elucidation of the interaction mode between their active binding sites and their potent ligands is rather difficult. The comparison of selected ligands is thus an indirect approach which could help to determine the pharmacophore elements. In the present work, ligands for the benzodiazepine receptors are characterized using electron density maps at medium resolution, reconstructed from calculated structure factors using crystallography simulation programs. As the obtained threedimensional maps are rather complex, they then can be simplified by a topological analysis in order to represent the ligands as connected graphs. An original genetic algorithm method is finally elaborated and implemented to carry out graph comparison. The design of the algorithm implies appropriate and efficient coding and evaluation of the generated graph superimpositions. The major aim of this study consists in determining the nature and arrangement of the molecular fragments taking part in the binding of ligands to their benzodiazepine receptor sites.
| Original language | English (US) |
|---|---|
| Title of host publication | Computer-Assisted Lead Finding and Optimization: Current Tools for Medicinal Chemistry |
| Publisher | wiley |
| Pages | 497-509 |
| Number of pages | 13 |
| ISBN (Print) | 9783906390406, 3906390160, 9783906390161 |
| DOIs | |
| State | Published - May 18 2007 |
| Externally published | Yes |
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Keywords
- Benzodiazepine receptor pharmacophore
- Comparison of molecular models
- Genetic algorithm method
ASJC Scopus subject areas
- Chemistry(all)
- Chemical Engineering(all)
Cite this
Development of a Genetic Algorithm Method Especially Designed for the Comparison of Molecular Models : Application to the Elucidation of the Benzodiazepine Receptor Pharmacophore. / Meurice, Nathalie; Leherte, Laurence; Vercauteren, Daniel P.; Bourguignon, Jean Jacques; Wermuth, Camille G.
Computer-Assisted Lead Finding and Optimization: Current Tools for Medicinal Chemistry. wiley, 2007. p. 497-509.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - Development of a Genetic Algorithm Method Especially Designed for the Comparison of Molecular Models
T2 - Application to the Elucidation of the Benzodiazepine Receptor Pharmacophore
AU - Meurice, Nathalie
AU - Leherte, Laurence
AU - Vercauteren, Daniel P.
AU - Bourguignon, Jean Jacques
AU - Wermuth, Camille G.
PY - 2007/5/18
Y1 - 2007/5/18
N2 - Since the three-dimensional molecular structure of the benzodiazepine receptors is not yet univoquely known, the direct elucidation of the interaction mode between their active binding sites and their potent ligands is rather difficult. The comparison of selected ligands is thus an indirect approach which could help to determine the pharmacophore elements. In the present work, ligands for the benzodiazepine receptors are characterized using electron density maps at medium resolution, reconstructed from calculated structure factors using crystallography simulation programs. As the obtained threedimensional maps are rather complex, they then can be simplified by a topological analysis in order to represent the ligands as connected graphs. An original genetic algorithm method is finally elaborated and implemented to carry out graph comparison. The design of the algorithm implies appropriate and efficient coding and evaluation of the generated graph superimpositions. The major aim of this study consists in determining the nature and arrangement of the molecular fragments taking part in the binding of ligands to their benzodiazepine receptor sites.
AB - Since the three-dimensional molecular structure of the benzodiazepine receptors is not yet univoquely known, the direct elucidation of the interaction mode between their active binding sites and their potent ligands is rather difficult. The comparison of selected ligands is thus an indirect approach which could help to determine the pharmacophore elements. In the present work, ligands for the benzodiazepine receptors are characterized using electron density maps at medium resolution, reconstructed from calculated structure factors using crystallography simulation programs. As the obtained threedimensional maps are rather complex, they then can be simplified by a topological analysis in order to represent the ligands as connected graphs. An original genetic algorithm method is finally elaborated and implemented to carry out graph comparison. The design of the algorithm implies appropriate and efficient coding and evaluation of the generated graph superimpositions. The major aim of this study consists in determining the nature and arrangement of the molecular fragments taking part in the binding of ligands to their benzodiazepine receptor sites.
KW - Benzodiazepine receptor pharmacophore
KW - Comparison of molecular models
KW - Genetic algorithm method
UR - http://www.scopus.com/inward/record.url?scp=84951798015&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84951798015&partnerID=8YFLogxK
U2 - 10.1002/9783906390406.ch32
DO - 10.1002/9783906390406.ch32
M3 - Chapter
SN - 9783906390406
SN - 3906390160
SN - 9783906390161
SP - 497
EP - 509
BT - Computer-Assisted Lead Finding and Optimization: Current Tools for Medicinal Chemistry
PB - wiley
ER -