Computational study of the conformational ensemble of CX3C chemokine receptor 1 (CX3CR1) and its interactions with antagonist and agonist ligands

The CX3C chemokine receptor 1 (CX3CR1), a member of the class A of G Protein-Coupled Receptors (GPCR) superfamily, and its ligand fractalkine constitute an important biochemical axis that influence many cellular pathways involving homeostatic and inflammatory processes. They participate in the activation, chemotaxis and recruitment of multiple immunological cells such as microglia, macrophages and monocytes, and play a critical role in neuroinflammatory conditions such as Alzheimer's disease and multiple sclerosis, in the recovery from central nervous system injuries, in several chronic, peripheral inflammatory entities and in some infective processes including HIV-AIDS. In this work we present the study of the CX3CR1 receptor employing extensive atomistic Molecular Dynamics (MD) simulations with the aim to characterize the conformational ensemble of the receptor in the presence of its antagonist and agonist ligands. We analyzed the receptor conformational changes and described interactions within its key regions and the bounded ligands to identify their notable differences. Finally, we classify the features that would allow the identification of patterns that characterize a functional state to contribute to the understanding of the complexity of the GPCR superfamily.