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Online ISSN: 1860-7187
January 15, 2010
VIP: Selective Pharmacophore Models of Dopamine D1 and D2 Full Agonists Based on Extended Pharmacophore Features
Marcus Malo, Lars Brive, Kristina Luthman, Peder Svensson*
Dopamine D1 and D2 receptors play critical roles in CNS function, and so gathering detailed knowledge about the structural features required for full agonist activity and selectivity at these receptors is very important. In their Full Paper, Svensson and colleagues propose new D1 and D2 pharmacophore models based on features that represent receptor interaction points. These models provide a better understanding of the structural characteristics responsible for the selectivity of D1 and D2 agonists. The reasons behind such selectivity can be attributed to both geometrical differences in the arrangement of the features and shape differences covered by the different sets of excluded volumes. This work provides useful information for the design of new D1 and D2 agonists and also for comparative homology modeling of D1 and D2 receptors. The approach is general and can therefore be applied to other ligand–protein interactions for which no experimental protein structure is available.
Received September 23, 2009; published online January 13, 2010, DOI: 10.1002/cmdc.200900398.