Figure - available from: Frontiers in Chemistry
This content is subject to copyright.
Source publication
Hydrogen bonds play a critical role in nucleobase studies as they encode genes, map protein structures, provide stability to the base pairs, and are involved in spontaneous and induced mutations. Proton transfer mechanism is a critical phenomenon that is related to the acid–base characteristics of the nucleobases in Watson–Crick base pairs. The ene...
Similar publications
![PES scans for cyclohexane‐MR3 and benzene‐MR3[10] M= As (green), Sb...](publication/353688290/figure/fig1/AS:11431281244837274@1716008313321/PES-scans-for-cyclohexane-MR3-and-benzene-MR310-M-As-green-Sb-blue-and-Bi_Q320.jpg)
The noncovalent interactions of heavy pnictogens with π‐arenes play a fundamental role in fields like crystal engineering or catalysis. The strength of such bonds is based on an interplay between dispersion and donor/acceptor interactions, and is generally attributed to the presence of π‐arenes. Computational studies of the interaction between the...
Citations
... With five natural nucleobase monomers (G, C, A, and T/U), DNA and RNA are able to store and transfer a rich density of genetic information with high fidelity [1,2]. Nonetheless, the diversity of biological populations arises from processes of natural selection and genetic variation [3,4], the latter of which is influenced by mutations that occur during DNA replication [5,6]. Even with the precise replication process [7], including proofreading [8] and DNA repair [8], the mutation rate still typically reaches 10 −9 ∼ 10 −12 per base pair synthesized [9]. ...
... In the Watson-Crick (WC) model, nucleobase pairs are in their "keto" form [12] rather than their "imino" or "enol" forms. Mispairs are believed to commonly arise from tautomeric shifts in the nucleobases [5,6] that cause a change in the hydrogen bond pattern at the Watson-Crick edge without changing the charge [2]. These rare nucleobase tautomers are able to form WC-like mispairs that can sometimes circumvent proofreading and repair machinery and lead to mutations and misincorporation in DNA replication [7,9] and translation [13]. ...
... There have been a number of quantum mechanical studies that have investigated the tautomerization of nucleobases in DNA and RNA [2,6,25,[46][47][48][49][50][51] as well as extended synthetic genetic alphabets [2] that have great promise in the development of new technology. There have been fewer computational studies that utilize QM/MM simulations [23,52] to characterize the tautomerization reaction free energy path in complex condensed-phase environments. ...
Rare tautomeric forms of nucleobases can lead to Watson–Crick-like (WC-like) mispairs in DNA, but the process of proton transfer is fast and difficult to detect experimentally. NMR studies show evidence for the existence of short-time WC-like guanine–thymine (G-T) mispairs; however, the mechanism of proton transfer and the degree to which nuclear quantum effects play a role are unclear. We use a B-DNA helix exhibiting a wGT mispair as a model system to study tautomerization reactions. We perform ab initio (PBE0/6-31G*) quantum mechanical/molecular mechanical (QM/MM) simulations to examine the free energy surface for tautomerization. We demonstrate that while the ab initio QM/MM simulations are accurate, considerable sampling is required to achieve high precision in the free energy barriers. To address this problem, we develop a QM/MM machine learning potential correction (QM/MM-ΔMLP) that is able to improve the computational efficiency, greatly extend the accessible time scales of the simulations, and enable practical application of path integral molecular dynamics to examine nuclear quantum effects. We find that the inclusion of nuclear quantum effects has only a modest effect on the mechanistic pathway but leads to a considerable lowering of the free energy barrier for the GT*⇌G*T equilibrium. Our results enable a rationalization of observed experimental data and the prediction of populations of rare tautomeric forms of nucleobases and rates of their interconversion in B-DNA.
... Moreover, the unzipping DNA is a complex biological process and involves strong interactions from several proteins 22 . It has been hotly debated for decades if the coherence of tautomers can survive the unzipping helicase [23][24][25] . McFadden and Al-khalili modeled a specific mutational process involving proton tunneling and investigated the possibility of the coherence to be maintained. ...
... Thus the entanglement between mRNA and DNA survives for a longer time. In contrast, the environments with similar properties (the (24) � 11 =α 2 � 14 =αβ * e −Ŵ 1 t/2 e −Ŵ 2 t/2 e +i� 1 t e +i� 2 t www.nature.com/scientificreports/ near values for i s and Ŵ i s) cause more rapid decoherence. ...
The adaptive mutation phenomenon has been drawing the attention of biologists for several decades in evolutionist community. In this study, we propose a quantum mechanical model of adaptive mutation based on the implications of the theory of open quantum systems. We survey a new framework that explain how random point mutations can be stabilized and directed to be adapted with the stresses introduced by the environments according to the microscopic rules dictated by constraints of quantum mechanics. We consider a pair of entangled qubits consist of DNA and mRNA pair, each coupled to a distinct reservoir for analyzing the spreed of entanglement using time-dependent perturbation theory. The reservoirs are physical demonstrations of the cytoplasm and nucleoplasm and surrounding environments of mRNA and DNA, respectively. Our predictions confirm the role of the environmental-assisted quantum progression of adaptive mutations. Computing the concurrence as a measure that determines to what extent the bipartite DNA-mRNA can be correlated through entanglement, is given. Preventing the entanglement loss is crucial for controlling unfavorable point mutations under environmental influences. We explore which physical parameters may affect the preservation of entanglement between DNA and mRNA pair systems, despite the destructive role of interaction with the environments.
... As for the internal dynamics of DNA, the proton transfer between the two bases of the base-pairs that connect the two strands [39] (and references therein) has been much studied. The dynamics between the stacked bases has been studied mainly in presence of electric charges where charge transfer in DNA can be classified as hole transfer through oxidation of a nucleobase by adjacent radical cation or transfer of excess electrons through reduction of a nucleobase by an adjacent radical anion [40] (and references therein). ...
In this article, we investigate the propagation of an intrinsic (not environmental) perturbation along the DNA chain. In particular, the conditions were sought so that a perturbation, in addition to moving in a coherent and complete manner, remained enclosed within a DNA fragment for a life time similar to those of biological interest of hundreds of picoseconds or in the time scale of nanoseconds. The conditions of closure of these pieces of DNA and the conditions of prolongation of the life time of the perturbation have allowed us to introduce the concept of time-island for the base-pairs sequences with these characteristics. The amount of such time-islands in human chromosomes and their coding parts has been calculated, and their uneven distribution has been highlighted. Finally, we study pieces of DNA made up of numerous replicas, as in the Huntington’s disease. These systems with a number of replicas of the tens of units are, in fact, time-islands, albeit different from the simple ones already studied. By increasing the number of replicas, however, these time-islands tend to disappear because the coherence of the movement of the perturbation within them is lost. In this perspective, Huntington’s disease, and other similar diseases, could be interpreted as the loss of a time-island.
... Hydrogen bonding interactions are essential in many areas of physics, chemistry and biology, 1-3 and because of their unique physicochemical properties, they are central in many important processes such as, for example, single and double proton transfer reactions in nucleobases, 4,5 formation of low-barrier hydrogen bonds in proteins, [6][7][8] and proton-coupled electron transfer reactions in electrocatalysis. 9,10 In addition, the strength of the interactions within the hydrogen bonding network is vital to maintain the structural and thermodynamic stability of the system. ...
Hydrogen bonding interactions are essential in the structural stabilization and physicochemical properties of complex molecular systems, and carboxylic acid functional groups are common participants in these motifs. Consequently, the neutral formic acid (FA) dimer has been extensively investigated in the past, as it represents a useful model system to investigate proton donor-acceptor interactions. The analogous deprotonated dimers, in which two carboxylate groups are bound by a single proton, have also served as informative model systems. In these complexes, the position of the shared proton is mainly determined by the proton affinity of the carboxylate units. However, very little is known about the nature of the hydrogen bonding interactions in systems containing more than two carboxylate units. Here we report a study on the deprotonated (anionic) FA trimer. IR spectra are recorded in the 400-2000 cm-1 spectral range by means of vibrational action spectroscopy of FA trimer ions embedded in helium nanodroplets. Characterization of the gas-phase conformer and assignment of the vibrational features is achieved by comparing the experimental results with electronic structure calculations. To assist in the assignments, the 2H and 18O FA trimer anion isotopologues are also measured under the same experimental conditions. Comparison between the experimental and computed spectra, especially the observed shifts in spectral line positions upon isotopic substitution of the exchangeable protons, suggests that the prevalent conformer, under the experimental conditions, exhibits a planar structure that resembles the crystalline structure of formic acid.
... In biology, quantum effects may be important at the interfaces of tissues and biomolecules. For example, there is evidence that DNA mutations are prominently driven by tunneling of protons between bases [10] while photosynthesis and magnetoreception is driven by effects of the sub-atomic scales. ...
The main mechanism of energy storage at the nanoscale remains the electric double layer (EDL) composed of a charged surface and a diffuse layer of opposite charge with quantum treatment often being neglected. We recently showed that charged Fermi gas between two oppositely charged and equal plane-parallel planes results in a repulsive force between them. Here, we present a new branch of solutions to the same variational problem resulting in overall higher energy densities and find cases where the force between two like-charged surfaces is attractive and of the order of piconewtons per square nanometer. We find that the corresponding solutions' differential capacitance is on the order of classic Poisson-Boltzmann theory of the EDL. These results may be significant in biological systems where adhesion and interaction between charged surfaces is ubiquitous.
... However, multiple studies have argued that the tautomeric lifetime is much shorter than this timescale. 11,12 The timescale for which the tautomeric forms of base pairs can exist depends on the stability of the energetic minimum that the tautomeric forms exhibit. ...
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 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.
... Experiments performed in Escherichia (E.) Coli grown in deuterium oxide-enriched media showed decreased spontaneous mutation rate; considering that quantum tunneling probability is inversely correlated with the mass of the particle, replacement of the normal hydrogen atom from the DNA with its heavier isotope deuterium reduces the probability of this quantum phenomenon, so that the results observed in E. Coli cultured in deuterated environment suggest a role played by diminution of quantum tunneling (Srivastava, 2019). ...
Biological processes and physiological functions in living beings are featured by oscillations with a period of about 24 h (circadian) or cycle at the second and third harmonic (ultradian) of the basic frequency, driven by the biological clock. This molecular mechanism, common to all kingdoms of life, comprising animals, plants, fungi, bacteria, and protists, represents an undoubted adaptive advantage allowing anticipation of predictable changes in the environmental niche or of the interior milieu. Biological rhythms are the field of study of Chronobiology. In the last decade, growing evidence hints that molecular platforms holding up non-trivial quantum phenomena, including entanglement, coherence, superposition and tunnelling, bona fide evolved in biosystems. Quantum effects have been mainly implicated in processes related to electromagnetic radiation in the spectrum of visible light and ultraviolet rays, such as photosynthesis, photoreception, magnetoreception, DNA mutation, and not light related such as mitochondrial respiration and enzymatic activity. Quantum effects in biological systems are the field of study of Quantum Biology. Rhythmic changes at the level of gene expression, as well as protein quantity and subcellular distribution, confer temporal features to the molecular platform hosting electrochemical processes and non-trivial quantum phenomena. Precisely, a huge amount of molecules plying scaffold to quantum effects show rhythmic level fluctuations and this biophysical model implies that timescales of biomolecular dynamics could impinge on quantum mechanics biofunctional role. The study of quantum phenomena in biological cycles proposes a profitable “entanglement” between the areas of interest of these seemingly distant scientific disciplines to enlighten functional roles for quantum effects in rhythmic biosystems.
... Quantum biology was established in the 1920s and studies how the subatomic world of quantum mechanics plays a role in living cells. Current advances in research have identified phenomena like proton tunnelling, where the proton spontaneously disappears from one location within the cellular atom to another location, as a potential for disease propagation [87,88]. What allows such a phenomenon to occur is that the human DNA molecule is a helical structure with disulfidee bridges and hydrogen atoms arranged at its periphery. ...
... These hydrogen atoms are protons and as a consequence could be observed in protonic exchanges across the helical structure. In fact, quantum proton tunnelling was identified as occurring at room temperature in DNA and has been hypothesized as a cause for cancer formation as this process can be propagated as mutations that arise during DNA replication [87]. Whether this contributes to an association with oncological disease states like Glioblastoma multiforme and others remains to be explored, but is an area of potential research enquiry. ...
... The cellular machinery shows errors during DNA replication. These errors generate mutations that affect health disorders as cancer (Srivastava, 2019). Two types of mutations appear during this DNA replication: induced mutations due to external agents, and spontaneous mutations. ...
... Two types of mutations appear during this DNA replication: induced mutations due to external agents, and spontaneous mutations. As an origin of these spontaneous point mutations arising in DNA (Brovarets' et al., 2012;Srivastava, 2019) has been considered the prototropic tautomerism of nucleotide bases. As the detection of the different tautomer forms appears difficult, this tautomeric assumption has been studied by different computational approaches (Danilov et al., 2005) and in some cases confirmed experimentally (Bebenek et al., 2011;Wang et al., 2011). ...
Proton transfer reactions are a widespread phenomenon in many areas of the life sciences and it is one of the origins of the spontaneous point mutations during DNA replication. Because of its importance, many studies have been reported on these reactions. However, the present work is the first one focused on the structural geometrical changes by double proton transfer (DPT). Thus, different Watson–Crick (WC) pairs were optimized first in a simple model with one nucleoside base pair, and in a microhelix form with three nucleoside base pairs. The canonical and few tautomeric forms were considered in DNA:DNA microhelices with A-type and B-type helical forms. The stability of these structures and how the DPT process affects the main geometrical parameters was analyzed, in particular the deformation of the helical parameters. The M06-2X DFT method was used for this purpose. The purine/pyrimidine ring in the keto form appears easier to be deformed than when it is in the enol form. The weaker WC base pair formed with mixed microhelices than with nucleobases alone and the significant deformation of the helical and backbone parameters with the DPT appears to complicate this process in microhelices.
Communicated by Ramaswamy H. Sarma
... Quantum biology was established in the 1920s and studies how the subatomic world of quantum mechanics plays a role in living cells. Current advances in research have identified phenomena like proton tunnelling, where the proton spontaneously disappears from one location within the cellular atom to another location, as a potential for disease propagation [87,88]. What allows such a phenomenon to occur is that the human DNA molecule is a helical structure with disulfidee bridges and hydrogen atoms arranged at its periphery. ...
... These hydrogen atoms are protons and as a consequence could be observed in protonic exchanges across the helical structure. In fact, quantum proton tunnelling was identified as occurring at room temperature in DNA and has been hypothesized as a cause for cancer formation as this process can be propagated as mutations that arise during DNA replication [87]. Whether this contributes to an association with oncological disease states like Glioblastoma multiforme and others remains to be explored, but is an area of potential research enquiry. ...
