title: The use of G-protein coupled receptor models in lead optimization.
abstract: With the emerging new crystal structures of G-protein coupled receptors (GPCRs), the number of reported in silico receptor models vastly increases every year. The use of these models in lead optimization (LO) is investigated here. Although there are many studies where GPCR models are used to identify new chemotypes by virtual screening, the classical application in LO is rarely reported. The reason for this may be that the quality of a model, which is appropriate for atomistic modeling, must be very high, and the biology of GPCR ligand-dependent signaling is still not fully understood. However, the few reported studies show that GPCR models can be used efficiently in LO for various problems, such as affinity optimization or tuning of physicochemical parameters.
authors.affiliation: Computational Chemistry, Lead Identification & Optimization Support Unit, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany. christofer.tautermann@boehringer-ingelheim.com
authors.forename: Christofer S
authors.initials: CS
authors.lastname: Tautermann
mesh_terms: D015195:Drug Design; D057166:High-Throughput Screening Assays; D008958:Models, Molecular; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry
chemical_list: D043562:Receptors, G-Protein-Coupled; D054852:Small Molecule Libraries