In-vitro selection of novel GPCR ligands

G-protein coupled receptors are one of the largest membrane receptor families in mammals. Members of this group bind to a wide variety of ligands and regulate a multitude of bodily functions. Thus, they are major targets for existing drugs and still of great interest to the pharmaceutical industry. However, despite all this attention, existing medications target only ~10% of known GPCRs, and ~12% of human GPCRs are still without a known natural ligand or are orphaned. De-orphanization of GPCRs was a major research subject in the past, and it still retains its topicality, but a variety of technical and biological difficulties have slowed the research pace on this subject, and novel de-orphanization strategies are urgently needed. In this article, we demonstrate that the employment of natural selection in a setting where microorganism growth is dependent on receptor activation could provide a solution and increase the pace of novel GPCR ligand discovery.