INVESTIGADORES
PERUCHENA Nelida Maria
congresos y reuniones científicas
Título:
Non-covalent interactions in ligand-receptor complexes. A study by electron charge density
Autor/es:
ANGELINA, EMILIO; ANDUJAR, S; SUVIRE, F. D.; ENRIZ, D. R.; PERUCHENA, N. M.
Lugar:
Foz do Iguazu
Reunión:
Congreso; 12th Latin American Conference on Physical Organic Chemistry; 2013
Institución organizadora:
Latin American Physical Organic Chemistry
Resumen:
One of the most motivating fact for study of the non-covalent
interactions is that they are responsible for the structure and dynamics and,
consequently, also the function of biological macromolecules. Thus, for example
the interaction of a hormone with a receptor can produce a cascade of processes
many of them closely related to the formation or rupture of non-covalent
interactions. Then, the understanding of non-covalent interactions in
biomolecules and their microsolvated clusters in the gas phase, constituted a
bulky challenge. In addition, as the non covalent interactions become weaker than
covalent interactions they are more difficult to describe properly. However,
recent advances in computational calculation of the electron charge density make
possible the proper description of the three-dimensional network of bonding and
non bonding interactions in the context of the quantum theory of atoms in
molecules (QTAIM). In fact, nowdays it is well know
that the stacking of aromatic ring of amino acids in proteins is evidently much
more important than it has been previously believed and, indeed, can form one
of the dominant stabilizing contributions.
In this work, several selected
conformations of molecular complexes, obtained from our ¡°reduced model system¡± 1
(with only 13 amino acids of the active site of the receptor) were used as
input by the calculation of the charge density. Single point calculations were
realized with Gaussian 03 employing a hybrid B3LYP functional and 6-31+G(d,p)
as a basis set.
The results show that the interactions of the catechol OH DA in differentconformations of the complex DA-RD2, determine the
decrease (or increase) of the electron density on the aromatic ringof DA. In turn,
the electronic population of the aromatic ring of DA, defines its
orientation within the active site and the type of interactions that are
established with the aromatic
rings of the receptor. The stacking-type interactions between the C¥ð¨ù C¥ð ring and the aromatic rings DA receptor,
are favored when onthe ring ofDA is diminished. Conversely, when the electronic charge on the ring of DA is high, this tends to orient perpendicular(T-shaped) to the plane of the aromatic rings of
the receiver, verifying ¥ð- interactions C-H...C¥ð type.
Summarizing, in this paper we reported the results obtained by charge
density analysis of the network of non covalent interactions present in the
active site of the receptor (in relevant
conformations of L-R complexes). We believe that our results could help in the
understanding the contribution that a particular amino acid present in the
active site of the receptor could make on the network of weak non covalent
interactions and this knowledge can serve as a guide for the design of new
ligands for this receptor.
1 Andujar et al. Journal
of Chemical Information and Modelling, 2012,
52, 99-112.