Accelerating GPCR drug discovery through computation and experiment integrated with direct detection of ligand binding events

We present a perspective on an integrated workflow for GPCR drug discovery that combines computational modeling, functional cellular assays, and FLOWER, a label-free ultra-sensitive optical biosensing system for quantitating direct ligand receptor binding. We use bitter and sweet taste receptors (TAS2Rs and T1R2/T1R3) as examples of how FLOWER resolves receptor activation mechanisms left ambiguous after in silico screening and cell assays. This workflow offers a generalizable strategy for accelerating the discovery of selective and mechanism informed GPCR targeting therapeutics.