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

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 B₄, 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.