C8 - Development of modulators at the chemokine-like receptor to elucidate its role in obesity

Previously, we were able to identify the binding mode of the chemerin, a 14 kDa adipokine with its receptor CMKLR1 by using Rosetta as a computational design tool. The binding mode is based on results of CMKLR1 mutagenesis studies, substitution of amino acids within the C-terminal nonapeptide as well as identified cyclic peptide agonists. Now, we will screen for antagonists and modulators of CMKLR1 to reveal orthosteric ligands as well as allosteric modulators and potentiators by high throughput screening, rational design and combine the results with computational design.