Understanding the rules of life is one of the most important scientific endeavours and has revolutionised both biology and biotechnology. Remarkable advances in observation techniques allow us to investigate a broad range of complex and dynamic biological processes in which living systems could exploit quantum behaviour to enhance and regulate biological functions. Recent evidence suggests that these non-trivial quantum mechanical effects may play a crucial role in maintaining the non-equilibrium state of biomolecular systems. Quantum biology is the study of such quantum aspects of living systems. In this review, we summarise the latest progress in quantum biology, including the areas of enzyme-catalysed reactions, photosynthesis, spin-dependent reactions, DNA, fluorescent proteins, and ion channels. Many of these results are expected to be fundamental building blocks towards understanding the rules of life.
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.
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29 January 2021 in Physical Chemistry Chemical Physics
Proton transfer along the hydrogen bonds of DNA can lead to the creation of short-lived, but biologically relevant point mutations that can further lead to gene mutation and, potentially, cancer.
Proton transfer between the DNA bases can lead to mutagenic Guanine-Cytosine tautomers. Over the past several decades, a heated debate has emerged over the biological impact of tautomeric forms. Here, we determine that the energy required for generating tautomers radically changes during the separation of double-stranded DNA. Density Functional Theory calculations indicate that the double proton transfer in Guanine-Cytosine follows a sequential, step-like mechanism where the reaction barrier increases quasi-linearly with strand separation. These results point to increased stability of the tautomer when the DNA strands unzip as they enter the helicase, effectively trapping the tautomer population. In addition, molecular dynamics simulations indicate that the relevant strand separation time is two orders of magnitude quicker than previously thought. Our results demonstrate that the unwinding of DNA by the helicase could simultaneously slow the formation but significantly enhance the stability of tautomeric base pairs and provide a feasible pathway for spontaneous DNA mutations.
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23 December 2022 in The Journal of Physical Chemistry Letters