Quantum tunnelling in DNA
Tunnelling is a quantum phenomenon in which a particle is able to access a classically forbidden region. This often manifests as a “hopping” motion in which it appears that a particle has overcome an energy barrier which is greater than its kinetic energy. Studying quantum systems allows us to determine tunnelling rates and decide whether it is likely to happen.
In 1964, it was proposed by Per-Olov Löwdin  that quantum tunnelling can occur within the hydrogen bonds joining Watson-Crick nucleotide pairs. Since then, quantum tunneling has been explored as a mechanism at work in enzyme catalysis , olfaction , and other biological processes. Here at the Leverhulme Quantum Biology Doctoral Training Centre we use open quantum systems and density functional theory amongst other theoretical tools to make predictions about tunneling rates, and have experiments running in parallel to try and detect tunneling in the lab.
The 1964 work by Löwdin  proposes that there is a non-zero probability that the protons in hydrogen bonds holding together the two strands of DNA in the Watson-Crick model  can tunnel from one nucleotide to the other, dramatically altering the bond length. This spontaneous position shift transforms a base pair form the canonical to the tautomeric form. This causes an error in the genetic code, and accumulated errors of this kind could be responsible for mutation, ageing, and - in extreme cases - tumour formation. The work at the Leverhulme Centre builds on previous work carried out at Surrey .
In order to model this system, an open quantum systems  approach which uses the Caldeira-Leggett master equation  to describe the interaction of the proton in the hydrogen bond, the backbone of the DNA structure, and the surrounding cellular aqueous environment. Density functional theory is used to calculate the shape of the potential due to the DNA backbone. After solving the master equation, we explore the sensitivity of tunneling rates due to the form of the environmental interaction, the asymmetry of the backbone potential, and the ``memory" retained by the environment. Although working closely together, Sapphire will focus on the mathematical behaviour described by the Caldeira-Leggett master equation and Louie will focus on the chemical properties of the DNA structure.
Inspired by the experiments that demonstrated the importance of proton tunnelling in enzyme catalysis , Antonio and Virginia are currently investigating whether a similar kinetic isotope effect can alter the spontaneous mutation rate. If quantum tunnelling is involved in the transition of a DNA base from the common to its rare tautomeric form, then replacing a hydrogen nucleus (a single proton) with a deuterium nucleus (consisting of a proton and a neutron) should slow the transition rate since quantum tunnelling will be highly sensitive to doubling the mass of the particle trying to tunnel. By using deuterated water (D2O) as solvent rather than H2O and employing advanced experimental techniques from molecular biology, they aim to explore a potential relation between proton tunnelling and mutations.
 Löwdin PO. Proton tunneling in DNA and its biological implications. Reviews of Modern Physics. 1963 Jul 1;35(3):724.
 Devault D, Parkes JH, Chance B. Electron tunnelling in cytochromes. Nature. 1967 Aug;215(5101):642.
 Bittner ER, Madalan A, Czader A, Roman G. Quantum origins of molecular recognition and olfaction in Drosophila. The Journal of Chemical Physics. 2012 Dec 14;137(22):22A551.
 Watson JD, Crick FH. Molecular structure of nucleic acids. Nature. 1953 Apr 25;171(4356):737-8.
 Godbeer AD, Al-Khalili JS, Stevenson PD. Modelling proton tunnelling in the adenine–thymine base pair. Physical Chemistry Chemical Physics. 2015;17(19):13034-44.
 Breuer HP, Petruccione F. The theory of open quantum systems. Oxford University Press on Demand; 2002.
 Caldeira AO, Leggett AJ. Path integral approach to quantum Brownian motion. Physica A: Statistical mechanics and its Applications. 1983 Sep 1;121(3):587-616.
 Klinman JP, Offenbacher AR. Understanding biological hydrogen transfer through the lens of temperature dependent kinetic isotope effects. Accounts of chemical research. 2018 Aug 28;51(9):1966-74.