INVESTIGADORES
PUNGITORE Carlos Rodolfo
artículos
Título:
In silico study of the inhibition of DNA polymerase by a novel catalpol derivative
Autor/es:
MARTIN OA; GARRO HA; KURINA SANZ MB; PUNGITORE CR; TONN CE
Revista:
JOURNAL OF MOLECULAR MODELING - (Print)
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2011 vol. 17 p. 2717 - 2723
ISSN:
1610-2940
Resumen:
In this work, a novel catalpol derivative
(6,10,2′,6′-tetraacetyl-O-catalpol), which was previously
obtained by our group and shown experimentally to inhibit
a type of Taq DNA polymerase, was studied in silico.
Studies of the interaction of 6,10,2′,6′-tetraacetyl-O-catalpol
with the Klentaq fragment of the Taq DNA polymerase I
from Thermus aquaticus helped to elucidate the mechanism
of inhibition of the enzyme, and offered valuable information
that can be used to propose substrate structural
modifications aimed at increasing the binding affinity.
Classical and semi-empirical methods were used to
characterize the conformational preferences of this organic
compound in solution. Using docking simulations,
the most probable binding mode was found, and the
stabilities of the docked solutions were tested in a series
of molecular dynamics experiments. Results indicated
that the mechanism of inhibition may be competitive,
which agrees with previous binding experiments done
with 6,10,2′,6′-tetraacetyl-O-catalpol.