Subtype-selective mechanisms of negative allosteric modulators binding to group I metabotropic glutamate receptors.

ABSTRACT: Group I metabotropic glutamate receptors (mGlu₁ and mGlu₅) are promising targets for multiple psychiatric and neurodegenerative disorders. Understanding the subtype selectivity of mGlu₁ and mGlu₅ allosteric sites is essential for the rational design of novel modulators with single- or dual-target mechanism of action. In this study, starting from the deposited mGlu₁ and mGlu₅ crystal structures, we utilized computational modeling approaches integrating docking, molecular dynamics simulation, and efficient post-trajectory analysis to reveal the subtype-selective mechanism of mGlu₁ and mGlu₅ to 10 diverse drug scaffolds representing known negative allosteric modulators (NAMs) in the literature. The results

SUBMITTER: Fu TT 

PROVIDER: S-EPMC8285414 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature