Non-covalent interactions in receptor-ligand complexes. A study based on the electron charge density

In this paper, we reported the results obtained by charge density analysis of the network of non-covalent interactions (NCI) established in the binding pocket of a receptor, in relevant conformations of ligand – receptor complexes. Starting with strong and moderate hydrogen bonds, moving on to weake...

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Detalles Bibliográficos
Autores: Angelina, Emilio Luis, Andujar, Sebastian Antonio, Tosso, Rodrigo David, Enriz, Ricardo Daniel, Peruchena, Nelida Maria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/35831
Acceso en línea:http://hdl.handle.net/11336/35831
Access Level:acceso abierto
Palabra clave:Dft
D2-Dopamine Receptor
Nbo
Qtaim
Stacking Interaction
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descripción
Sumario:In this paper, we reported the results obtained by charge density analysis of the network of non-covalent interactions (NCI) established in the binding pocket of a receptor, in relevant conformations of ligand – receptor complexes. Starting with strong and moderate hydrogen bonds, moving on to weaker polar interactions and ending with stacking and T-shape like interactions between aromatic rings, all of them have been investigated within the framework of the density functional theory and the quantum theory of atoms in molecules. Also, natural bond orbital analysis was carried out, in order to evaluate quantitatively the electronic population of the aromatic rings. The analysis of our “case study” shows that the interactions of the catechol OH groups of the ligand, in the different conformations of the dopamine (DA) – D2 receptor complex, determine the decrease or increase of the electron density on the aromatic ring of DA. In turn, the electronic population of the aromatic ring of DA defines its orientation within the binding site and the type of interactions that it establishes with the aromatic rings of the receptor. Although the approach used here was traditionally applied to the study of NCI in small molecules complexes in gas phase, we show through this work that this methodology is also a very powerful tool for the study of biomolecular complexes, providing a very detailed description of the binding event.