| Popis: |
G-protein-coupled receptors (GPCRs) are the largest superfamily of human membrane proteins. They serve as the primary targets for ∼1/3 of currently marketed drugs. Although large chemical databases containing tens of millions of commercially available compounds are provided, it is impractical for academia and industry to perform high-throughput screening to test all the compounds experimentally. In this regard, virtual screening and computer-aided drug discovery have proven useful in selecting a small subset of promising compounds for experimental testing and reducing the cost in biomedical research of GPCRs. Here, we review applications of computational modeling for discovery of novel small-molecule GPCR ligands, including antagonists, agonists, biased agonists, and allosteric modulators. The remaining challenges for computer-aided drug discovery in GPCRs are discussed as well. |
