Professor Jim Al-Khalili CBE FRS HonFREng HonFInstP HonFIET

Proton transfer across hydrogen bonds in DNA can produce non-canonical nucleobase dimers and is a possible source of single-point mutations when these forms mismatch under replication. Previous computational studies have revealed this process to be energetically feasible for the guanine-cytosine (GC) base pair, but the tautomeric product (G * C *) is short-lived. In this work we reveal, for the first time, the direct effect of the replisome enzymes on proton transfer, rectifying the shortcomings of existing models. Multi-scale quantum mechanical/molecular dynamics (QM/MM) simulations reveal the effect of the bacterial PcrA Helicase on the double proton transfer in the GC base pair. It is shown that the local protein environment drastically increases the activation and reaction energies for the double proton transfer, modifying the tautomeric equilibrium. We propose a regime in which the proton transfer is dominated by tunnelling, taking place instantaneously and without atomic rearrangement of the local environment. In this paradigm, we can reconcile the metastable nature of the tautomer and show that ensemble averaging methods obscure detail in the reaction profile. Our results highlight the importance of explicit environmental models and suggest that asparagine N624 serves a secondary function of reducing spontaneous mutations in PcrA Helicase.

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.

In the midst of the COVID-19 pandemic, science is crucial to inform public policy. At the same time, mistrust of scientists and misinformation about scientific facts are rampant. Six scientists, actively involved in outreach, reflect on how to build a better understanding and trust of science. In the midst of the COVID-19 pandemic, science is crucial to inform public policy. At the same time, mistrust of scientists and misinformation about scientific facts are rampant. Six scientists, actively involved in outreach, reflect on how to build a better understanding and trust of science. Katie Mack is a theoretical astrophysicist exploring a range of questions in cosmology, the study of the universe from beginning to end. She is currently an assistant professor of physics at North Carolina State University. Her first popular book, The End of Everything (Astrophysically Speaking) , will be out in August. She can be found on Twitter as @AstroKatie. Karl Kruszelnicki is a science generalist, with an enthusiastic public following in Australia. He has frontlined in multiple media for decades. He is writing his 46th book and does half a dozen science Q&A radio shows every week. He is a Fellow in the School of Physics at the University of Sydney. He has degrees in maths and physics, biomedical engineering, medicine and surgery. He can be found on Twitter as @doctorkarl. Lisa Randall studies theoretical particle physics and cosmology at Harvard University. Her research connects theoretical insights to puzzles in our current understanding of the properties and interactions of matter. Additionally, she engages with the public through her popular science books, articles, lectures, and radio and TV appearances. Jess Wade is an excitable scientist with an enthusiasm for equality. By day, she is based in the Department of Chemistry at Imperial College London, where she creates superthin films out of organic electronic materials that emit and absorb circularly polarized light. She spends her evenings editing Wikipedia, working to make the internet less sexist and racist. She can be found on Twitter as @jesswade. Jim Al-Khalili, FRS, is a theoretical physicist, author and broadcaster. He holds a Distinguished Chair in physics at the University of Surrey, where he teaches and conducts his research in nuclear physics and open quantum systems. As well as his popular science writing, he is a regular presenter on TV and hosts the long-running BBC Radio 4 programme, The Life Scientific . His latest book, The World According to Physics , is out now. He can be found on Twitter as @jimalkhalili. Vlatko Vedral is a professor of physics at Oxford and National University of Singapore working on quantum physics. He has received many awards for his work, including the Royal Society Wolfson Research Merit Award and the World Scientific Medal and Prize, and was elected a Fellow of the Institute of Physics in 2017. He gives regular interviews to the media and has written articles for New Scientist , Scientific American and other major newspapers, as well as two popular science books.

The misincorporation of a noncomplementary DNA base in the polymerase active site is a critical source of replication errors that can lead to genetic mutations. In this work, we model the mechanism of wobble mispairing and the subsequent rate of misincorporation errors by coupling first principles quantum chemistry calculations to an open quantum systems master equation. This methodology allows us to accurately calculate the proton transfer between bases, allowing the misincorporation and formation of mutagenic tautomeric forms of DNA bases. Our calculated rates of genetic error formation are in excellent agreement with experimental observations in DNA. Furthermore, our quantum mechanics/molecular mechanics model predicts the existence of a short-lived "tunnelling ready " configuration along the wobble reaction pathway in the polymerase active site, dramatically increasing the rate of proton transfer by a hundredfold, demonstrating that quantum tunnelling plays a critical role in determining the transcription error frequency of the polymerase.

The adenine-thymine tautomer (A*-T*) has previously been discounted as a spontaneous mutagenesis mechanism due to the energetic instability of the tautomeric configuration. We study the stability of A*-T* while the nucleobases undergo DNA strand separation. Our calculations indicate an increase in the stability of A*-T* as the DNA strands unzip and the hydrogen bonds between the bases stretch. Molecular Dynamics simulations reveal the time scales and dynamics of DNA strand separation and the statistical ensemble of opening angles present in a biological environment. Our results demonstrate that the unwinding of DNA, an inherently out-of-equilibrium process facilitated by helicase, will change the energy landscape of the adenine-thymine tautomerization reaction. We propose that DNA strand separation allows the stable tautomeriza-tion of adenine-thymine, providing a feasible pathway for genetic point mutations via proton transfer between the A-T bases.

A widely accepted practice for treating deuteron breakup in A(d,p)B reactions relies on solving a three-body A+n+p Schrödinger equation with pairwise A−n, A−p and n−p interactions. However, it was shown in Phys. Rev. C 89, 024605 (2014) that projection of the many-body A+2 wave function into the three-body A+n+p channel results in a complicated three-body operator that cannot be reduced to a sum of pairwise potentials. It contains explicit contributions from terms that include interactions between the neutron and proton via excitation of the target A. Such terms are normally neglected. We estimate the first-order contribution of these induced three-body terms and show that applying the adiabatic approximation to solving the A+n+p model results in a simple modification of the two-body nucleon optical potentials. We illustrate the role of these terms for the case of 40Ca(d,p)41Ca transfer reactions at incident deuteron energies of 11.8, 20, and 56 MeV, using several parametrizations of nonlocal optical potentials.

Quantum biology is usually considered to be a new discipline, arising from recent research that suggests that biological phenomena such as photosynthesis, enzyme catalysis, avian navigation or olfaction may not only operate within the bounds of classical physics but also make use of a number of the non-trivial features of quantum mechanics, such as coherence, tunnelling and, perhaps, entanglement. However, although the most significant findings have emerged in the past two decades, the roots of quantum biology go much deeper—to the quantum pioneers of the early twentieth century. We will argue that some of the insights provided by these pioneering physicists remain relevant to our understanding of quantum biology today.

The beta decay of Li-11 has been investigated at TRIUMF-ISAC using a high-efficiency array of Compton suppressed HPGe detectors. From a line-shape analysis of the Doppler-broadened peaks observed in the Be-10 gamma spectrum, both the half-lives of states in Be-10 and the energies of the beta-delayed neutrons feeding those states were obtained. Furthermore, it was possible to determine the excitation energies of the parent states in Be-11 with uncertainties comparable to those obtained from neutron spectroscopy experiments. These data suggest that the beta decay to the 8.81 MeV state in Be-11 occurs in the Li-9 core and that one neutron comprising the halo of Li-11 survives in a halolike configuration after the beta-delayed neutron emission from this level.

The principle that mutations occur randomly with respect to the direction of evolutionary change has been challenged by the phenomenon of adaptive mutations. There is currently no entirely satisfactory theory to account for how a cell can selectively mutate certain genes in response to environmental signals. However, spontaneous mutations are initiated by quantum events such as the shift of a single proton (hydrogen atom) from one site to an adjacent one. We consider here the wave function describing the quantum state of the genome as being in a coherent linear superposition of states describing both the shifted and unshifted protons. Quantum coherence will be destroyed by the process of decoherence in which the quantum state of the genome becomes correlated (entangled) with its surroundings. Using a very simple model we estimate the decoherence times for protons within DNA and demonstrate that quantum coherence may be maintained for biological time-scales. Interaction of the coherent genome wave function with environments containing utilisable substrate will induce rapid decoherence and thereby destroy the superposition of mutant and non-mutant states. We show that this accelerated rate of decoherence may significantly increase the rate of production of the mutated state.

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 decoher-ent 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.

Model uncertainties arising due to suppression of target excitations in the description of deuteron scattering and resulting in a modification of the two-body interactions in a three-body system are investigated for several (d,p) reactions serving as indirect tools for studying the astrophysical (p,γ) reactions relevant to rp process. The three-body nature of the deuteron-target potential is treated within the adiabatic distorted-wave approximation (ADWA) which relies on a dominant contribution from the components of the three-body deuteron-target wave function with small n−p separations. This results in a simple prescription for treating the explicit energy dependence of two-body optical potentials in a three-body system requiring nucleon optical potentials to be evaluated at a shifted energy with respect to the standard value of half the deuteron incident energy. In addition, the ADWA allows for leading-order multiple-scattering effects to be estimated, which leads to a simple renormalization of the adiabatic potential's imaginary part by a factor of two. These effects are assessed using both nonlocal and local optical potential systematics for 26Al, 30P, 34Cl, and 56Ni targets at a deuteron incident energy of 12 MeV, which is typical for experiments with radioactive beams in inverse kinematics. The model uncertainties induced by the three-body nature of deuteron-target scattering are found to be within 40% both in the main peak of angular distributions and in total (d,p) cross sections. At higher deuteron energies, around 60 MeV, model uncertainties can reach 100% in the total cross sections. A few examples of application to astrophysically interesting proton resonances in 27Si and 57Cu obtained using (d,p) reactions and mirror symmetry are given.

The contribution of a three-nucleon (3N) force, acting between the neutron and proton in the incoming deuteron with a target nucleon, to the deuteron-target potential in the entrance channel of the A(d, p)B reaction has been calculated within the adiabatic distorted wave approximation (ADWA). Four different 3N interaction sets from local chiral effective field theory (χEFT) at next-to-next-to-leading order (N2LO) were used. Strong sensitivity of the adiabatic deuteron-target potential to the choice of the 3N force format has been found, which originates from the enhanced sensitivity to the short-range physics of nucleon-nucleon (NN) and 3N interactions in the ADWA. Such a sensitivity is reduced when a Watanabe folding model is used to generate d-A potential instead of ADWA. The impact of the 3N force contribution on (d, p) cross sections depends on assumptions made about the p-A and n-A optical potentials used to calculate the distorted d-A potential in the entrance channel. It is different for local and nonlocal optical potentials and depends on whether the induced three-body force arising due to neglect of target excitations is included or not.

Understanding the behaviour of a quantum system coupled to its environment is of fundamental interest in the general field of quantum technologies. It also has important repercussions on foundational problems in physics, such as the process of decoherence and the so-called quantum measurement problem. There have been many approaches to explore Markovian and non-Markovian dynamics within the framework of open quantum systems, but the richness of the ensuing dynamics is still not fully understood. In this paper we develop a non-Markovian extension of the standard Caldeira-Leggett model, based on expanding the dynamics of the reduced system at high temperature in inverse powers of the high-frequency cutoff of the Ohmic spectral density of the environment and derive a non-Markovian master equation for the reduced density matrix for the case of a general potential. We also obtain a fully analytical solution in the free particle case. While the short-time behavior of this solution does not diverge substantially from the Markovian behavior, at intermediate times we find a resurgence of coherence, which we name lateral coherence. We identify this with a corresponding transient negative entropy production rate, which is understood to be characteristic of non-Markovian dynamics. We also analyze the positivity of the reduced density matrix and derive the corresponding Fokker-Planck equation in the classical limit.

The adenine-thymine tautomer (A*-T*) has previously been discounted as a spontaneous mutagenesis mechanism due to the energetic instability of the tautomeric configuration. We study the stability of A*-T* while the nucleobases undergo DNA strand separation. Our calculations indicate an increase in the stability of A*-T* as the DNA strands unzip and the hydrogen bonds between the bases stretch. Molecular Dynamics simulations reveal the timescales and dynamics of DNA strand separation and the statistical ensemble of opening angles present in a biological environment. Our results demonstrate that the unwinding of DNA, an inherently out-of-equilibrium process facilitated by helicase, will change the energy landscape of the adenine-thymine tautomerisation reaction. We propose that DNA strand separation allows the stable tautomerisation of adenine-thymine, providing a feasible pathway for genetic point mutations via proton transfer between the A-T bases.

Proton transfer between DNA bases can lead to mutagenic tautomers, but as their lifetimes are thought to be much shorter than DNA separation times their role during the DNA replication cycle is often overlooked. Here, the authors model the separation of the DNA base pair guanine-cytosine using density functional theory and find increased stability of the tautomer when the DNA strands unzip as they enter a helicase enzyme, effectively trapping the tautomer population. 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.

This is the third volume in a series of Lecture Notes based on the highly succesful Euro Summer School on Exotic Beams.

This book is about my own personal favourite puzzles and conundrums in science, all of which have famously been referred to as paradoxes, but which turn out not to be paradoxes at all when considered carefully and viewed from the right ...

In this compelling, inspiring book, Jim al-Khalili celebrates the forgotten pioneers whohelped shape our understanding of the world.All scientists have stood ...

The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process, β-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.