Computational modeling of oxytocin-receptors interactions with the common marmoset Callithrix jacchus Pro8OT variant

The oxytocinergic system plays a crucial role in regulating physiological and behavioral processes, making it a key component of neurobiology in both humans and animals. This study utilizes computational modeling to explore the interaction between G protein-coupled receptors (GPCRs) and the Homo sapiens neurohormone oxytocin (Leu8OT), as well as, for the first time, the Pro8OT variant found in Callithrix jacchus and other New World monkeys. Pro8OT has been previously recognized for its functional and evolutionary significance. We performed homology modeling of receptors (OTR, VTR1a, and VTR1b) in both human and marmoset species. Additionally, cholesterol's role in modulating receptor binding and stability was evaluated in our simulations. Our findings suggest a general pattern across primates, preserving the essential pleiotropic functions of the oxytocinergic system in regulating physiology and behavior, which align with the shared evolutionary framework of species within this order. However, some specific variations were observed, as Pro8OT exhibits distinct binding affinities and unique receptor interactions. Comparative analysis of human and marmoset OT-OTR complexes indicate a more stable and favorable binding environment in marmoset systems, suggesting species-specific adaptations. These results enhance our understanding of the oxytocinergic system, bridging computational models with evolutionary neurobiology and providing insights for future functional studies.