G-protein coupled receptors (GPCR) are a diverse group of cell surface receptors that bind ligands, undergo a conformational change, and initiate an intracellular signaling cascade through binding to a G-protein. The receptor group binds to molecules of a vast chemical space and is known to have regulatory role in functions ranging from growth sensation to hormone responses. This research investigates the chemical environment and hardness of GPCR active sites through protein visualization, electronic structure calculations, and experimental docking analysis using molecules from chemical informatics database with known inhibitory potentials. Based on the hard-soft acid-base principle, it is hypothesized that the GPCR active site is predominately soft in nature due to its location within the cell membrane; however, several critical polar residues likely optimize ligand orientation. Characterization of this chemical environment will inform future drug design and research to optimize inhibition potential of GPCR receptors.
