**7. Conclusions**

This review was devoted to tight-binding (TB) modeling of nucleic acid sequences like DNA and RNA. We briefly presented the TB approach and discussed its various submodels: wire, ladder, extended ladder, fishbone (wire), and fishbone ladder. We addressed various types of orders (periodic, quasiperiodic, fractal) or disorder (diagonal, non-diagonal, random, methylation) and explained how these various types of order or disorder affect charge transport. We proceeded to a discussion of aperiodicity, quasicrystals and the mathematics of aperiodic substitutional sequences. Specifically, we discussed the notions of primitive substitutions, Perron–Frobenius eigenvalue, induced substitutions, and Pisot property. We explained how the energy structure of nucleic acid wires is affected by order or disorder. We also discussed the corresponding transmission coefficients, focusing on the effects of coupling the nucleic acids to external leads, and demonstrating that, apart from the internal degree of order or disorder of a given sequence, there are several other factors that can significantly affect their charge transport properties. We also discussed the effects that various types of order or disorder induce on the current–voltage curves and presented some efforts aiming to examine the potentiality to utilize the charge transport characteristics of nucleic acids as a tool to probe several diseases or disorders. The sensitivity that the results demonstrate regarding the choice of the nucleic acids sequence, the recruited models and parametrizations, the way the systems are coupled to external leads, the nature of the leads, the environmental conditions, etc, indicate that much work is needed in order to reach a thorough description of the effect the combination such a multitude of factors has on charge transport. Furthermore, other factors, such as the sequence geometry or the use of modified

nitrogenous bases could be potentially used to tailor the above-mentioned properties of nucleic acids and analogues.

**Author Contributions:** Conceptualization, K.L. and C.S.; methodology, K.L. and C.S.; software, K.L. and C.S.; validation, K.L. and C.S.; formal analysis, K.L. and C.S.; investigation, K.L. and C.S.; resources, K.L. and C.S.; data curation, K.L. and C.S.; writing—original draft preparation, K.L.; writing—review and editing, C.S.; visualization, K.L. and C.S.; supervision, C.S.; project administration, C.S.; funding acquisition, K.L. and C.S.

**Funding:** This research was surpported by the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under the HFRI PhD Fellowship gran<sup>t</sup> (GA no 260).

**Conflicts of Interest:** The authors declare no conflict of interest.
