Design of low molecular weight ligands for the TSH receptor utilizing its sequence homology to the LH receptor

On the Applicability of GPCR Homology Models to Computer-Aided Drug Discovery: A Comparison between In Silico and Crystal Structures of the β2-Adrenergic Receptor

“…Homology models of GPCRs, especially those supported by experimental data, and molecular docking experiments have been widely used in computational medicinal chemistry to guide site-directed mutagenesis and for drug discovery purposes, pursued also through virtual screenings and through the generation of docking-based quantitative structure–activity relationship (QSAR) models. – Encouraging results led to a general acceptance of these models, which, however, although corroborated by indirect experimental evidence, could not be ultimately validated. The recent publication of the crystal structure of the human β 2 -AR proved conclusively that GPCRs indeed share a very structurally conserved 7TM core, strongly supporting the body of literature and the hypotheses that were built on the basis of homology modeling and molecular docking. – …”