Omega-3 DHA as a blank canvas : A molecular approximation to how lipid mediators modulate LGR6 in inflammation resolution

The leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6) has a potential role in inflammation resolution and different cancer processes. In this study, we employed computational techniques, including molecular docking and molecular dynamics simulations of mammalian membrane-embeded systems, to understand the activation mechanism of LGR6 upon binding of the specialized pro-resolving lipid mediator maresin 1. Additionally, we investigated the interaction and the dynamics of other relevant lipid mediators (leukotriene B, protectin D1, and docosahexaenoic acid) to understand their influence on receptor activity. Our findings reveal different mediator-specific conformational changes in LGR6, suggesting hydroxyl positions at these mediators as the key factor by which maresin 1 and other lipid mediators modulate receptor activation and contribute to inflammation resolution.