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Conformational and electronic study of dopamine interacting with the D 2 dopamine receptor
Author(s) -
Tosso Rodrigo D.,
Parravicini Oscar,
Zarycz M. Natalia C.,
Angelina Emilio,
Vettorazzi Marcela,
Perucheélida,
Andujar Sebastián,
Enriz Ricardo D.
Publication year - 2020
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.26361
Subject(s) - chemistry , dopamine , molecule , ligand (biochemistry) , quantum , electronic structure , potential energy surface , computational chemistry , chemical physics , receptor , physics , quantum mechanics , organic chemistry , biochemistry , neuroscience , biology
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.