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ABSTRACT: Among the distinct strategies proposed to expand the genetic alphabet, size-expanded nucleobases are promising for the development of modified DNA duplexes with improved biotechnological properties. In particular, duplexes built up by replacing canonical bases with the corresponding benzo-fused counterparts could be valuable as molecular nanowires. In this context, this study reports the results of classical molecular dynamics simulations carried out to examine the structural and dynamical features of size-expanded DNAs, including both hybrid duplexes containing mixed pairs of natural and benzo-fused bases (xDNA) and pure size-expanded (xxDNA) duplexes. Furthermore, the electronic structure of both natural and size-expanded duplexes is examined by means of density functional computations. The results confirm that the structural and flexibility properties of the canonical DNA are globally little affected by the presence of benzo-fused bases. The most relevant differences are found in the enhanced size of the grooves, and the reduction in the twist. However, the analysis also reveals subtle structural effects related to the nature and sequence of benzo-fused bases in the duplex. On the other hand, electronic structure calculations performed for xxDNAs confirm the reduction in the HOMO-LUMO gap predicted from the analysis of the natural bases and their size-expanded counterparts, which suggests that pure size-expanded DNAs can be good conductors. A more complex situation is found for xDNAs, where fluctuations in the electrostatic interaction between base pairs exerts a decisive influence on the modulation of the energy gap.
The Journal of Physical Chemistry A 09/2011; 115(41):11344-54. · 2.95 Impact Factor
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ABSTRACT: Melting temperatures of DNA duplexes containing the phenoxazine (P) and G-clamp (X) cytosine analogues exhibited a strong and unusual dependence on the nucleoside flanking the modified nucleobase, and the same trend was observed in PNA-DNA duplexes incorporating X in the PNA chain. Molecular dynamics simulations of the DNA duplexes show that generalized stacking (including secondary interactions of the ammonium group of X) and hydrogen bonding are good descriptors of the different duplex stabilities.
Organic Letters 11/2007; 9(22):4503-6. · 5.86 Impact Factor
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ABSTRACT: The tautomeric properties of benzoderivatives of the canonical nucleic acid bases have been studied by using different computational approaches. Attention has been paid to the impact of the benzene group in altering the tautomeric preferences of the canonical bases both in the gas phase and in aqueous solution. To this end, relative solvation free energies of the tautomers determined from Self-Consistent Reaction Field continuum calculations and Monte Carlo-Free Energy Perturbation are combined with gas-phase tautomerization free energies determined from quantum mechanical calculations. The results provide a detailed picture of the tautomeric preferences of the benzoderivatives of nucleic acid bases. This information is used to examine the recognition properties of the preferred tautomers of the benzo-fused derivatives, paying particular attention to the ability to form Watson-Crick hydrogen-bonding and stacking interactions as well as to the hydrophobic nature of the modified bases. The implications of present results on the potential use of benzo-fused bases as potential building blocks in modified DNA duplexes are examined.
The Journal of Physical Chemistry A 02/2006; 110(2):510-8. · 2.95 Impact Factor
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ABSTRACT: The essential dynamics of different normal and chemically modified DNA duplexes pertaining to the B family have been extensively explored from molecular dynamics simulations using powerful data mining techniques. Some of them, which are presented here for the first time, might become standard, powerful tools to characterize the dynamical behavior of complex biomolecular structures such as nucleic acids. Their potential impact is illustrated by examining the extended trajectories sampled for the set of DNA duplexes considered in this study, which allows us to discuss the degree of conservation of the natural flexibility pattern of the different DNAs, which in specific cases contain severe chemical modifications.
06/2005;
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ABSTRACT: The tautomeric properties of isoguanine (also named 2-oxoadenine or 2-hydroxyadenine) have been studied in the gas phase, in different pure solvents, and in the DNA environment using state of the art theoretical methods. Our results show that isoguanine constitutes an unique example of how tautomerism can be modulated by the environment. Compared to the tautomeric preference in the gas phase, both polar solvents and the DNA microenvironment dramatically change the intrinsic tautomeric properties of isoguanine. Tautomers which are important in physiological conditions are less than 1/10(5) of the total population of isoguanine in the gas phase. The impact of the present findings in the understanding of spontaneous mutations and in the design of new nucleobases with multiple recognition properties is discussed.
Journal of the American Chemical Society 02/2004; 126(1):154-64. · 9.91 Impact Factor
