The biologically active conformations of ligand CCKB receptor

摘要

We analyzed literature data about structures of ligands of CCKB receptor. The structure of the binding site (fragments of the third extracellular loop and the seventh transmembrane helix of CCKB receptor) was determined recently by experiments. We were finding presumable biologically active conformations (BAC) of the ligands by two methods. One of them is based on the fact that the most stable conformations of the biologically active peptide on the phase interface "water-lipophilic medium" are often similar to the BAC. Another method is based on the formation of the stable ligand-receptor complex during the modeling procedure. We used Monte-Carlo method with the fixed geometry of the receptor and the optimized geometry of tetrapeptide cholecystokinin (CCK-4). It has been shown, that the first method should be used to find BAC of antagonists of CCKB receptor. The strategy of the formation of the stable ligand-receptor complex during the modeling procedure can be used for the designing of peptide agonists of CCKB receptor.