Design and Applications of Noncanonical DNA Base Pairs

Abstract

While the Watson-Crick base pairs are known to stabilize the DNA double helix and play a vital role in storage/replication of genetic information, their replacement with non-Watson-Crick base pairs has recently been shown to have interesting practical applications. Nowadays, theoretical calculations are routinely performed on very complex systems to gain a better understanding of how molecules interact with each other. We not only bring together some of the basic concepts of how mispaired or unnatural nucleobases interact with each other but also look at how such an understanding influences the prediction of novel properties and development of new materials. We highlight the recent developments in this field of research. In this Perspective, we discuss the success of DFT methods, particularly, dispersion-corrected DFT, for applications such as pH-controlled molecular switching, electric-field-induced stacking of disk-like molecules with guanine quartets, and optical birefringence of alkali-metal-coordinated guanine quartets. The synergy between theoretical models and real applications is highlighted.

How many tautomerization pathways connect Watson–Crick-like G*·T DNA base mispair and wobble mismatches?

“…3d), to which corresponds the torsion vibration of the NH 2 group of the G base with imaginary frequency ν і =-178.2i cm -1 . This fast (τ 99.9% =6.09·10 -8 s) (Table S2) and large amplitude quantum oscillation of the G·T(w 2 ) base mispair allows it to be incorporated into the structure of the DNA double helix, since its energy is significantly less than the energy of the stacking interactions of the neighbouring Watson-Crick DNA base pairs [80]. 11 The third novel G*·Т(WC)↔G·Т(w 2 ) pathway (Table 5 and Figs.…”

“…It is logical to suggest that the barrier of the G·Т(w)→G*·Т(WC) mutagenic tautomerisation of the wobble G·Т(w) base mispair in the recognition pocket of the DNA-polymerase reduces comparably with the isolated state, in particular, due to the stacking interactions [80]. Table 2) is much greater than the energy of the bases hydration by the corresponding sites of the interaction [85][86][87].…”

The effects of tautomerization and protonation on the adenine–cytosine mismatches: a density functional theory study

“…The experimental proof further substantiates the conceivability of an A-C mispair based pH switch. In addition, it has been observed that pHdependent molecular switches can be constructed harnessing the stability of a protonated A-C mispair (Jissy & Datta, 2014).…”

Thermodynamically feasible photoelectron transfer from bioactive π-expanded imidazole luminophores to ZnO nanocrystals

“…3 ZnO nanoparticles have unique physical and chemical properties and potential biomedical applications by virtue of their nontoxic nature, low cost, biosafety, biocompatibility and wide usage in daily life such as drug carriers, cosmetics, etc. [16][17][18][19][20] Nano ZnO prefers to bind with a ring nitrogen atom (N-site) relative to other binding sites of the DNA bases; the adsorption strength of ZnO with the N-site of guanine is much higher than that with other sites. 11 The photoactive surfaces of the nanoparticles produce reactive oxygen species that can potentially cause oxidative stress which leads to cellular protein, lipid and DNA damage.…”