Identification of Allosteric Modulators of Metabotropic Glutamate 7 Receptor Using Proteochemometric Modeling.
J Chem Inf Model
; 57(12): 2976-2985, 2017 12 26.
Article
em En
| MEDLINE
| ID: mdl-29172488
ABSTRACT
Proteochemometric modeling (PCM) is a computational approach that can be considered an extension of quantitative structure-activity relationship (QSAR) modeling, where a single model incorporates information for a family of targets and all the associated ligands instead of modeling activity versus one target. This is especially useful for situations where bioactivity data exists for similar proteins but is scarce for the protein of interest. Here we demonstrate the application of PCM to identify allosteric modulators of metabotropic glutamate (mGlu) receptors. Given our long-running interest in modulating mGlu receptor function we compiled a matrix of compound-target bioactivity data. Some members of the mGlu family are well explored both internally and in the public domain, while there are much fewer examples of ligands for other targets such as the mGlu7 receptor. Using a PCM approach mGlu7 receptor hits were found. In comparison to conventional single target modeling the identified hits were more diverse, had a better confirmation rate, and provide starting points for further exploration. We conclude that the robust structure-activity relationship from well explored target family members translated to better quality hits for PCM compared to virtual screening (VS) based on a single target.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Glutamato Metabotrópico
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Relação Quantitativa Estrutura-Atividade
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Regulação Alostérica
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Descoberta de Drogas
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article