Ligand and Structure Based Models for the Identification of Beta 2 Adrenergic Receptor Antagonists.
Curr Comput Aided Drug Des
; 11(3): 222-36, 2015.
Article
em En
| MEDLINE
| ID: mdl-26265253
ABSTRACT
Ligand bound beta 2 adrenergic receptor (ß2AR) crystal structures are in use for screening of compound libraries for identifying inducers and blockers. However, in case of G protein coupled receptors (GPCR), docking and binding energy (BE) calculations are not enough to discriminate agonist and antagonists. Absence of a reliable model for discriminating ß2AR antagonist is still a major hurdle. Docking of known antagonists and agonists into activated and ground state ß2AR revealed several key intermolecular interactions and H-bonding patterns, which in combination, emerged as a model for prediction of antagonists. Present study identifies an alternative binding orientation, within the binding pocket, for blockers and a minimum grid size to lessen the false positive predictions. Cluster analysis revealed structural variability among the antagonists and a conserved pattern in case of agonists. A combination of docking and structure activity relationship (SAR) model reliably discriminated antagonists. Based on key intermolecular interactions, a set of agonists and antagonists useful to SAR, quantitative structure activity relationship (QSAR) and pharmacophore modeling, has also been proposed for identifying antagonists.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Modelos Moleculares
/
Relação Quantitativa Estrutura-Atividade
/
Descoberta de Drogas
/
Antagonistas de Receptores Adrenérgicos beta 2
/
Ligantes
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article