In silico study of the inhibition of DNA polymerase by a novel catalpol derivative |
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Authors: | Martin Osvaldo A Garro Hugo A Kurina Sanz Marcela B Pungitore Carlos Rodolfo Tonn Carlos E |
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Institution: | (1) IMASL-CONICET, Universidad Nacional de San Luis. Ej?rcito, de los Andes 950, 5700 San Luis, Argentina;(2) INTEQUI-CONICET, Facultad de Qu?mica, Bioqu?mica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, 5700 San Luis, Argentina; |
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Abstract: | 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. |
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