We report an exhaustive conformational and electronic study on dopamine (DA) interacting with the D2 dopamine receptor (D2 DR). For the first time, the complete surface of the conformational potential energy of the complex DA/D2 DR is reported. Such a surface was obtained through the use of QM/MM calculations. A detailed study of the molecular interactions that stabilize and destabilize the different molecular complexes was carried out using two techniques: Quantum Theory of Atoms in Molecules computations and nuclear magnetic shielding constants calculations. A comparative study of the behavior of DA in the gas phase, aqueous solution, and in the active site of D2 DR has allowed us to evaluate the degree of deformation suffered by the ligand and, therefore, analyze how rustic are the lock-key model and the induced fit theory in this case. Our results allow us to propose one of the conformations obtained as the "biologically relevant" conformation of DA when it is interacting with the D2 DR.
Keywords: NMR calculations; QTAIM analysis; biologically relevant conformation; dopamine; molecular interactions; potential energy surface.
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