Molecular modelling study of the role of cholesterol in the stimulation ofthe oxytocin receptor

Cholesterol, an integral component of membranes in Eucaryota, is a modifier of membrane properties. In vivo studies have demonstrated that cholesterol can also modulate activities of some G protein-coupled receptors (GPCRs), which are integral membrane proteins. This can result either from an effect of cholesterol on the membrane fluidity or from specific interactions of t he membrane cholesterol with the receptor, as recently demonstrated for the cholecystokinin type beta (CCKR beta) or the oxytocin receptor (OTR). Usin g molecular modelling, we studied conformational preferences of cholesterol and several of its analogues. Subsequently, we simulated the distributions of their preferred conformations around the surface of OTR, CCKR beta and a chimeric oxytocin/cholecystokinin receptor. Consequently, we suggest resi dues on the surface of OTR which are potentially significant in the OTR/cho lesterol interaction.