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Conformational and electronic study of dopamine interacting with the D2 dopamine receptor |
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| Authors: | Rodrigo D. Tosso Oscar Parravicini M. Natalia C. Zarycz Emilio Angelina Marcela Vettorazzi Nélida Peruchena Sebastián Andujar Ricardo D. Enriz |
| Affiliation: | 1. Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina Instituto Multidisciplinario de Investigaciones Biológicas (IMIBIO-SL), CONICET, San Luis, Argentina;2. Laboratorio de Estructura Molecular y Propiedades, Facultad de Ciencias Exactas y Naturales y Agrimensura, Corrientes, Argentina Instituto de Química Básica y Aplicada (IQUIBA-NEA), CONICET, Corrientes, Argentina;3. Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina |
| Abstract: | We report an exhaustive conformational and electronic study on dopamine (DA) interacting with the D2 dopamine receptor (D2DR). For the first time, the complete surface of the conformational potential energy of the complex DA/D2DR 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 D2DR 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 D2DR. |
| Keywords: | biologically relevant conformation dopamine molecular interactions NMR calculations potential energy surface QTAIM analysis |