The pharmacological response of many class-A G-protein-coupled receptors are known to be modulated by sodium ions (Na+). For the dopamine D2-like receptors, consisting of the D2, D3, and D4 receptors (D2R, D3R, and D4R), a physiologically relevant level of Na+ (~100 mM) has been shown to decrease the affinities of the agonists including the endogenous agonist dopamine, while enhancing the affinities for some classes of antagonists, compared to those in the absence of Na+. To better understand the structural basis for the allosteric effects of Na+, we performed computational docking and molecular dynamics simulations of D2R and D3R in complex with Na+-sensitive and insensitive antagonists, and used comparative network analysis of the intramolecular interactions to derive the impact of Na+ on the conformational dynamics of the receptors and specifically to the ligand-binding site. Our analysis also suggests moieties of the ligands that are responsible for Na+-sensitivity.

Structural basis for Na<sup>+</sup>-sensitivity in dopamine D3 and D2 receptors

247th National Meeting (2014)

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Structural basis for Na+-sensitivity in dopamine D3 and D2 receptors

Structural basis for Na⁺-sensitivity in dopamine D3 and D2 receptors