Conformational and electronic study of dopamine interacting with the D 2 dopamine receptor.

Autor: Tosso RD; 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., Parravicini O; 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., Zarycz MNC; 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., Angelina E; 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., Vettorazzi M; 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., Peruchena N; 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., Andujar S; 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., Enriz RD; 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.
Jazyk: angličtina
Zdroj: Journal of computational chemistry [J Comput Chem] 2020 Aug 05; Vol. 41 (21), pp. 1898-1911. Date of Electronic Publication: 2020 Jun 08.
DOI: 10.1002/jcc.26361
Abstrakt: We report an exhaustive conformational and electronic study on dopamine (DA) interacting with the D 2 dopamine receptor (D 2 DR). For the first time, the complete surface of the conformational potential energy of the complex DA/D 2 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 D 2 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 D 2 DR.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: