GPCR fragment design: A case study of using drug discovery tools at mcule.com
G-protein-coupled receptors (GPCR) are attractive drug targets as their dysfunction can be associated with a large number of diseases. Several class “A” GPCR crystal structures have been recently published. Similar structural elements of these GPCRs suggest that GPCR ligands might share structural similarities. We developed a virtual screening protocol to assess GPCR-likeness of candidate molecules by structure-based docking.
X-ray structures for 6 therapeutically relevant GPCRs were available at the launch of the project: human beta2-adrenergic receptor (PDB ID: 2RH1), turkey beta1-adrenergic receptor (PDB ID: 2Y00), human histamine H1 receptor (PDB ID: 3RZE), human adenosine A2A receptor (PDB ID: 3EML), human dopamine D3 receptor (PDB ID: 3PBL), human chemokine CXCR4 receptor (PDB ID: 3ODU).