3D Pharmacophore, hierarchical methods, and 5-HT4 receptor binding data.
5-Hydroxytryptamine subtype-4 (5-HT(4)) receptors have stimulated considerable interest amongst scientists and clinicians owing to their importance in neurophysiology and potential as therapeutic targets. A comparative analysis of hierarchical methods applied to data from one thousand 5-HT(4) receptor-ligand binding interactions was carried out. The chemical structures were described as chemical and pharmacophore fingerprints. The definitions of indices, related to the quality of the hierarchies in being able to distinguish between active and inactive compounds, revealed two interesting hierarchies with the Unity (1 active cluster) and pharmacophore fingerprints (4 active clusters). The results of this study also showed the importance of correct choice of metrics as well as the effectiveness of a new alternative of the Ward clustering algorithm named Energy (Minimum E-Distance method). In parallel, the relationship between these classifications and a previously defined 3D 5-HT(4) antagonist pharmacophore was established.
Varin
Thibault
T
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Université de Caen, Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Caen Cedex, France.
Saettel
Nicolas
N
Villain
Jonathan
J
Lesnard
Aurelien
A
Dauphin
François
F
Bureau
Ronan
R
Rault
Sylvain
S
D000465:Algorithms; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D044422:Receptors, Serotonin, 5-HT4 / Q000737:chemistry*; D013329:Structure-Activity Relationship
D008024:Ligands; D044422:Receptors, Serotonin, 5-HT4