Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Optimizing charge transfer through G-quadruplex
The G-quadruplex is a quadruple helical form of nucleic acids that contains only the guanine (G) base in the quadruplex, while other bases can appear in loops. The unit constituent is the G-tetrad, a planar assembly of four guanines fortified by eight hydrogen bonds. The G-tetrads stack on top of each other in a G-quadruplex with a stacking distance of about 3.4 Å and a twist of about 30 degrees. Natural single-stranded G-rich sequences that occur in the telomeres and in other genomic regions can fold into G-quadruplexes. Polymorphism characterizes such G-quadruplexes: many different topologies are viable, depending on the sequence of glycosidic bond angles (Webba da Silva et al., 2009). Artificial G-quadruplexes can be synthesized by enzymatic procedures (Borovok et al., 2008).
An artificial G-quadruplex with four parallel strands and no edge loops, assembled by biotin-avidin recognition, is capable of conducting electrical charges over lengths of up to 100 nm when deposited on a hard substrate (Livshits et al., 2014). This is a revolutionary observation for nucleic acids and opens the way to nanotechnology applications. It is desirable to understand the electron transport mechanism and whether natural G-quadruplex motifs (parallel, antiparallel, hybrid) can discriminate between negligible and appreciable charge transfer between stacked tetrads.
In this presentation I will address these two issues. I will present first-principle calculations within density functional theory (DFT) of the inter-tetrad electronic coupling parameters for a structure that is a viable model of the molecules measured by Livshits et al. I will show that the computed transfer integral is effectively incorporated in an empirical hopping model that fits the experimental current-voltage characteristics with high precision. This explains the charge transport mechanism as a hopping process in which hopping centers are not necessarily a single G-tetrad but can be multi-tetrad. Furthermore, I will show the results of DFT calculations for several (~1000) G-quadruplex structures from the pdb database, interpreting that the parallel topology boosts inter-tetrad electronic coupling. In antiparallel or hybrid topologies, syn-anti and anti-syn glycosidic bond sequences impose structures that break electronic coupling. Finally, I will present a statistical analysis of structure-electronic correlations.
This research has been supported by the European Commission, the Italian Institute of Technology and Fondazione Cassa di Risparmio di Modena.
N. Borovok, N., Iram, N., Zikich, D., Ghabboun, J., Livshits, G. I., Porath, D., Kotlyar, A. B. (2008). Assembling of G-strands into novel tetra-molecular parallel G4-DNA nanostructures using avidin–biotin recognition. Nucleic Acids Res 36, 5050-5060.
G. I. Livshits, G. I., Stern, A., Rotem, D., Borovok, N., Eidelshtein, G., Migliore, A., Penzo, E., Wind, S. J., Di Felice, R., Skourtis, S. S., Cuevas, J. C., Gurevich, L., Kotlyar, A. B. & Porath, D. (2014). Long-range charge transport in single G-quadruplex DNA molecules. Nat Nanotech, in press. DOI: 10.1038/NNANO.2014.246.
Rosa Di Felice
Department of Physics and Astronomy