Designing Molecular Switches Based on DNA-Base Mispairing

Abstract

Stabilization of unstable mispairs on protonation in a DNA sequence can result in a change in the sequence conformation. Such sequences are being actively used for the synthesis of pH-driven molecular switches that have applications in biological pH sensing. We have studied various conformations of different mispairs of bases and their protonated forms using density functional theory (DFT) at B3LYP/6-31+G(d) and M05-2X/6-31+G(d,p) levels. Both gas-phase and aqueous-phase calculations are reported. Solvent phase calculations were done using the PCM and the COSMO solvation model. Our results show that the criterion for the protonation of a particular base in a mispair is not just its higher proton affinity. The planarity of the structure is significantly important, and a planar structure is energetically preferred over a bent mispair. Our calculations also show that the stabilization gained through protonation for the A-C, A-G, and the C-C mispairs is substantial (~20.0 kcal/mol); therefore, these are good candidates for pH-driven molecular switches.

Mesoscopic modeling of DNA denaturation rates: Sequence dependence and experimental comparison

“…Temperature driven DNA switches might give an easier reversible control to molecular operations than the pH driven switches that have been suggested in the literature. 40 Despite that mesoscopic DNA models are not yet sufficiently accurate for very reliable quantitative predictions, the qualitative trend that we predict based on relative denaturation rates is an interesting phenomenon that deserves experimental efforts to test it. However, measuring denaturation rates of dsDNA is an experimental tour-de-force.…”

Unexpected A·T(WC)↔A·T(rWC)/A·T(rH) and A·T(H)↔A·T(rH)/A·T(rWC) conformational transitions between the classical A·T DNA base pairs: A QM/QTAIM comprehensive study

“…Notably, that while it is known that DNA double helix contains the canonical Watson–Crick base pairs, which provides storage and precise transfer of the genetic information, their replacement with the non‐Watson–Crick base pairs leads to perspective interesting practical applications …”

Effect of external electric field on ground and singlet excited states of phenylalanine: A theoretical study

“…The effect of electric field on the chemical reactivity has been illustrated in several earlier studies [34][35][36][37][38][39][40][41][42][43][44]. Particularly, the chemical reactivity as a function of orientation in the electric field has been thoroughly investigated [34,35].…”

“…That the introduction of electric field influences both physical and chemical properties of various molecular systems are evident from these studies. Recently a number of works has been devoted to the study of application of external electric field on biological molecules [41][42][43][44].…”