Molecular dynamics simulations of the bis-intercalated complexes of ditercalinium and Flexi-Di with the hexanucleotide d(GCGCGC)2: theoretical analysis of the interaction and rationale for the sequence binding specificity

Journal of Medicinal Chemistry
B de Pascual-TeresaF Gago

Abstract

The X-ray crystal structures of the complexes of ditercalinium and Flexi-Di with d(CGCG)2 have been studied by computational chemistry methods in an attempt to rationalize their distinct structural features. In addition, the complexes of these two bisintercalating drugs with d(GCGCGC)2 have been modeled and subjected to 0.5 ns of molecular dynamics simulations in explicit solvent with the aim of evaluating the relative importance of hydrogen bonding and stacking interactions in the sequence binding specificity of these compounds. According to our calculations, the electrostatic term is attractive for the stacking interactions between the pyridocarbazole chromophores of these drugs and the base pairs that make up the sandwiched GpC step. On the contrary, this energy term is repulsive for the base pairs that make up the boundaries of the bisintercalation site. This differential electrostatic binding energy component, which is shown to have a strong orientational dependence, could lie at the origin of the observed binding preferences of these drugs. In addition, both the Lennard-Jones and the electrostatic energy terms contribute to stabilizing the underwound central GpC step. The attractive electrostatic interactions between the ...Continue Reading

References

May 25, 1977·Journal of Molecular Biology·F C BernsteinM Tasumi
Feb 1, 1992·Biopolymers·R A Friedman, B Honig
May 21, 1991·Biochemistry·F BarceloJ B Le Pecq
Nov 26, 1990·European Journal of Biochemistry·F HermanJ C Chottard
Dec 1, 1990·Biopolymers·R E Bruccoleri, M Karplus
May 1, 1989·Biopolymers·B JayaramB Honig
May 1, 1988·Journal of Medicinal Chemistry·P LéonB P Roques
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·I HusainA Sancar
Apr 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A DelbarreB P Roques
Feb 1, 1985·Journal of Biomolecular Structure & Dynamics·R Lavery, B Pullman
Mar 15, 1985·Science·D A PearlmanS H Kim
Jun 28, 1972·Biochemical and Biophysical Research Communications·S Arnott, D W Hukins
May 26, 1995·Science·B Honig, A Nicholls
Dec 23, 1994·Science·A Sancar
Mar 17, 1995·Journal of Molecular Biology·A A GorinW K Olson
Dec 16, 1994·Science·D M Crothers
Jan 1, 1994·Trends in Biochemical Sciences·S J MartinT G Cotter
Jan 1, 1993·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·B Van Houten, A Snowden
Apr 1, 1986·Journal of Computational Chemistry·Scott J WeinerDavid A Case

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Citations

Dec 5, 2002·Chembiochem : a European Journal of Chemical Biology·Carolina CarrascoChristian Bailly
Apr 8, 2006·Journal of Molecular Modeling·William N SetzerAnthony K Irvine
Oct 24, 2012·Future Medicinal Chemistry·Federico Gago
Jul 3, 2002·Biochemistry·Stephen D G CrowMichael J Waring

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