Abstract
Among the distinct strategies proposed to expand the genetic alphabet, sizeexpanded
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. Themost
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 HOMOLUMO 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.
