Integrated In Silico Fragment-Based Drug Design: Case Study with Allosteric Modulators on Metabotropic Glutamate Receptor 5.

ABSTRACT: GPCR allosteric modulators target at the allosteric binding pockets of G protein-coupled receptors (GPCRs) with indirect influence on the effects of an orthosteric ligand. Such modulators exhibit significant advantages compared to the corresponding orthosteric ligands, including better chemical tractability or physicochemical properties, improved selectivity, and reduced risk of oversensitization towards their receptors. Metabotropic glutamate receptor 5 (mGlu₅), a member of class C GPCRs, is a promising therapeutic target for treating many central nervous system diseases. The crystal structure of mGlu₅ in the complex with the negative allosteric modulator mavoglurant was recently reported, providing a fundamental model for designing new allosteric modulators. Computa

SUBMITTER: Bian Y 

PROVIDER: S-EPMC5836546 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature