- Selective structure-based virtual screening for full and partial agonists of the beta2 adrenergic receptor.
Selective structure-based virtual screening for full and partial agonists of the beta2 adrenergic receptor.
Journal of medicinal chemistry (2008-08-06)
Chris de Graaf, Didier Rognan
PMID18680279
ZUSAMMENFASSUNG
The recently solved high-resolution X-ray structure of the beta2 adrenergic receptor has been challenged for its ability to discriminate inverse agonists/antagonists from partial/full agonists. Whereas the X-ray structure of the ground state receptor was unsuitable to distinguish true ligands with different functional effects, modifying this structure to reflect early conformational events in receptor activation led to a receptor model able to selectively retrieve full and partial agonists by structure-based virtual screening. The use of a topological scoring function based on molecular interaction fingerprints was shown to be mandatory to properly rank docking poses and achieve acceptable enrichments for partial and full agonists only.
MATERIALIEN