Homology modeling of GPCR: oxytocin receptor
G-protein-coupled receptors (GPCRs) [1] are a large family of seven-transmembrane domain receptors that have been increasingly studied in recent years and are of big importance for several fields of science and farmaceutical industry. However, there are not many GPCRs with an experimentally determined structure at the atomic resolution. Oxytocin receptor is one of GPCRs which, by activating Gq proten - phospholipase C - inositol-1,4,5-triphosphate pathway, increases the cytoplasmic Ca2+ concentration. By binding to this receptor, oxytocin plays very important roles in sexual reproduction, labors, maternal bonding, and many emotional and social behaviors. Here, we used homology modelling [2, 3] to obtain a model of oxytocin receptor, based on the sequence simillarity with a receptor which does have a determined 3D struture. The model that we obtained was simulated in several different environments including the membrane build of 1-palmitoyl 2-oleoyl phosphatidylethanolamine molecules. By exploring the free energy surface of oxytocin, we have found distinctive energy minima which, we assume, correspond to different stable conformers of this hormone. One of the possible reasons for their existence could be found in the mechanism of oxytocins binding to its receptor. Therefore, the simulations included the oxytocin receptor - hormone interactions as well.
This project was supported by COST action GLISTEN (CM1207, LD14133) and GAČR (15-17269S). Access to computing and storage facilities MetaCentrum (LM2010005) and CERIT-SC (CZ. 1.05/3.2.00/08.0144) is greatly appreciated. Participation at the conference is supported by specific university research (MSMT No 21/2014).