1 research outputs found
Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach
We report here an exhaustive and complete conformational
study
on the conformational potential energy hypersurface (PEHS) of dopamine
(DA) interacting with the dopamine D2 receptor (D2–DR). A reduced
3D model for the binding pocket of the human D2–DR was constructed
on the basis of the theoretical model structure of bacteriorhodopsin.
In our reduced model system, only 13 amino acids were included to
perform the quantum mechanics calculations. To obtain the different
complexes of DA/D2–DR, we combined semiempirical (PM6), DFT
(B3LYP/6-31GÂ(d)), and QTAIM calculations. The molecular flexibility
of DA interacting with the D2–DR was evaluated from potential
energy surfaces and potential energy curves. A comparative study between
the molecular flexibility of DA in the gas phase and at D2–DR
was carried out. In addition, several molecular dynamics simulations
were carried out to evaluate the molecular flexibility of the different
complexes obtained. Our results allow us to postulate the complexes
of type A as the “biologically relevant conformations”
of DA. In addition, the theoretical calculations reported here suggested
that a mechanistic stepwise process takes place for DA in which the
protonated nitrogen group (in any conformation) acts as the anchoring
portion, and this process is followed by a rapid rearrangement of
the conformation allowing the interaction of the catecholic OH groups