An open quantum systems approach to proton tunnelling in DNA

Abstract

One of the most important topics in molecular biology is the genetic stability of DNA. One threat to this stability is proton transfer along the hydrogen bonds of DNA that could lead to tautomerisation, hence creating point mutations. We present a theoretical analysis of the hydrogen bonds between the Guanine-Cytosine (G-C) nucleotide, which includes an accurate model of the structure of the base pairs, the quantum dynamics of the hydrogen bond proton, and the influence of the decoherent and dissipative cellular environment. We determine that the quantum tunnelling contribution to the proton transfer rate is several orders of magnitude larger than the classical over-the-barrier hopping. Due to the significance of the quantum tunnelling even at biological temperatures, we find that the canonical and tautomeric forms of G-C inter-convert over timescales far shorter than biological ones and hence thermal equilibrium is rapidly reached. Furthermore, we find a large tautomeric occupation probability of 1.73 × 10−4, suggesting that such proton transfer may well play a far more important role in DNA mutation than has hitherto been suggested. Our results could have far-reaching consequences for current models of genetic mutations.

Proton transfer during DNA strand separation as a source of mutagenic guanine-cytosine tautomers

“…The bimodal distribution in the DNA separation events demonstrates a diverse and rich environment of energetic scenarios that are radically different from the idealised assumption made by previous authors, who either reduce the problem to a comparison of lifetimes disregarding the mechanisms of strand separation 4 , 7 , 9 , 10 , 18 , 19 or perform their calculations only in the static aqueous dimer 4 , 5 , 18 , 20 – 22 . Although several authors have pointed to the fact that the complex external environments may strongly determine the influence of tautomers on mutation 3 , 6 , 8 , 23 , our MD results show just how diverse the biological environment experienced by DNA is.…”

Quantum Tunnelling Effects in the Guanine-Thymine Wobble Misincorporation via Tautomerism

“…Recent theoretical work on the Watson–Crick bonded bases entering the helicase enzyme has shown that quantum effects lead to the formation of metastable tautomeric forms of DNA. , Quantum chemical models of G-C and A-T base pairs describe the double proton transfer’s potential energy surface (PES) in both canonical base pairs. The main difference between the A-T and G-C PES is that A-T has a considerable forward barrier for tautomer formation but a small reverse barrier that causes its tautomeric form to be unstable. − On the contrary, G-C has a sizable reverse barrier, giving a tautomeric lifetime comparable to that of the replication process.…”

“…Moreover, quantum tunnelling leads to a fast proton exchange between the bases, such that the time scale of the helicase cleavage is much slower than the proton transfer dynamics . Consequently, using a semiclassical interpretation, , the potentially mutagenic tautomer is continuously formed and destroyed over time scales several orders of magnitude quicker than that of helicase cleavage, after which, the bases are split into their monomeric forms. However, using a quantum interpretation, the tunnelling proton’s wave function evolve on a shorter time scale, so two probability distributions (in the canonical and tautomeric configuration) emerge.…”

Quantum Tunnelling Effects in the Guanine-Thymine Wobble Misincorporation via Tautomerisation

“…Recent theoretical work on the Watson-Crick bonded bases entering the helicase enzyme has shown that quantum effects lead to the formation of meta-stable tautomeric forms of DNA. 14,15 Quantum chemical models of G-C and A-T base pairs 14 describe the potential energy surface (PES) of the double proton transfer in both canonical base pairs. The main difference between the A-T and G-C PES is that A-T has a considerable forward barrier for the tautomer formation, but a small reverse barrier that causes its tautomeric form to be highly unstable.…”

“…Moreover, quantum tunnelling leads to a fast proton exchange between the bases, 19 such that the timescale of the helicase cleavage is much slower than the proton transfer dynamics. 7 Consequently, using a semi-classical interpretation, 14,15 the potentially mutagenic tautomeric form is continuously formed and destroyed over timescales several orders of magnitude quicker than the helicase cleavage, after which the bases are split into their monomeric forms. However, using a quantum interpretation, the tunnelling proton's wave functions evolve on a shorter timescale such that two clear probability distributions (in the canonical and tautomeric configuration) emerge.…”