Structural Modeling and in Silico Screening of Potential Small-Molecule Allosteric Agonists of a Glucagon-like Peptide 1 Receptor.

ABSTRACT: The glucagon-like peptide 1 receptor (GLP-1R) belongs to the pharmaceutically important class B family of G-protein-coupled receptors (GPCRs), and its incretin peptide ligand GLP-1 analogs are adopted drugs for the treatment of type 2 diabetes. Despite remarkable antidiabetic effects, GLP-1 peptide-based drugs are limited by the need of injection. On the other hand, developing nonpeptidic small-molecule drugs targeting GLP-1R remains elusive. Here, we first constructed a three-dimensional structure model of the transmembrane (TM) domain of human GLP-1R using homology modeling and conformational sampling techniques. Next, a potential allosteric binding site on the TM domain was predicted computationally. In silico screening of druglike compounds against this predicted allosteric site has id

SUBMITTER: Redij T 

PROVIDER: S-EPMC6648429 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature