Molecular Dynamics Simulation of Double Proton Transfer: Adenine–Thymine Base Pair

Marañon, Julio; Fantoni, A.C.; Grigera, J. Raúl

doi:10.1006/jtbi.1999.1008

Cited by 13 publications

(6 citation statements)

References 28 publications

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“…Specifically, barrier and reaction energies are similar to values of Gorb et al and Noguera et al for the concerted mechanism, and those of Xiao et al for the sptewise mechanism, shown in Table . In summary, our quantum values of reaction and activation energies are within the ranges that derive from published by other authors, specifically, from 10 to 14 kcal/mol for the reaction energy and of 12–23 kcal/mol for the energy barrier. Another concordance between our results and those collected in the literature is the asymmetry in the energy barrier of the process, being much more energetic in the sense of obtaining the A*‐T* tautomer than in the inverse case. In our case, the reverse process barrier is negligible (Δ

E_{s}^{‡}

< 1 kcal/mol) and the equilibrium constant is very small ( K eq ≈ 10 −10 ), which makes the few molecules of the rare tautomer easily revert to their canonical form and do not participate in the process of genetic mutation.…”

Section: Resultssupporting

confidence: 88%

“…There have been a large number of theoretical studies on this tautomerization process and its different mechanisms . Most of these studies addressed tautomerization in the gas phase using ab initio methods, although some authors employed a continuum model to describe the solvent.…”

Section: Introductionmentioning

confidence: 99%

“…Brovarets et al and Noguera et al compared the concerted and stepwise mechanisms for this process. Marañon et al observed that the influence of a medium with low dielectric constant on the taumerization process minimally modifies the energies. Cerón‐Carrasco et al dealt with proton transfer through explicit hydration with one or two water molecules and showed the important role played by these molecules, but they did not find stable tautomers.…”

Section: Introductionmentioning

confidence: 99%

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Theoretical thermodynamic study of the adenine-thymine tautomeric equilibrium: Electronic structure calculations and steered molecular dynamic simulations

2017

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Free energy of the tautomeric equilibrium A-T ! A*-T* between the canonical and noncanonical DNA base equilibrium in aqueous solution was theoretically determined by applying electronic structure methods (at the M06-2X-PCM/6-31111G(d,p) level) and steered molecular dynamic simulations. Concerted and stepwise mechanisms were considered for the double proton transfer in an effort to explain the anomalous behavior of this system where an unfavorable process without a transition state can be observed depending on the level of calculation used. Of the different mechanisms used in the simulations, the stepwise mechanism, in which the first step implies the transference of a proton from thymine to adenine, and a second step with the transference of a different proton from adenine to thymine, was the only one that showed two transition states and a reaction intermediate. However, a concerted and stepwise mechanism has similar kinetic and thermodynamic behavior, with similar reaction and activation energies. Simple proton transfer was more favorable for the transference of the hydrogen from the adenine to the thymine. The inclusion of an aqueous medium in this study only slightly modified these energies, but the barrier energy was higher when the solvent was described as a discrete medium. Transition states and intermediate structures were analyzed at molecular dynamic level. K E Y W O R D Sadenine-thymine, electronic structure calculation, proton transfer in solution, steered molecular dynamic simulations, tautomeric equilibrium, thermodynamic properties

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E_{s}^{‡}

Section: Resultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Theoretical thermodynamic study of the adenine-thymine tautomeric equilibrium: Electronic structure calculations and steered molecular dynamic simulations

2017

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“…7 Consequently, proton transfer mechanism in DNA base pairs have been extensively studied using a wide range theoretical methods. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] However, most of this studies were carried out in gas phase, though DNA properties are highly sensitive to the environment. Physiological conditions are obviously closer to the condensed phase than to the gas phase, and consequently studying (partially) hydrated DNA bases has become a very important task for computational chemists.…”

Section: Introductionmentioning

confidence: 96%

Effects of Hydration on the Proton Transfer Mechanism in the Adenine−Thymine Base Pair

Cerón‐Carrasco¹,

Requena²,

Michaux

et al. 2009

J. Phys. Chem. A

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We report the first density functional study of water catalytic effect in the double proton transfer (DPT) taking place in the adenine-thymine (AT) base pair. To gain more insight regarding the accuracy of several theoretical methods, the ability of various functionals and models for describing the geometry of this system has first been checked. According to our results, BP86/6-311++G(d,p) is the best option for describing the solvation effects in AT when applied to a two-water-molecule-featuring model. The two possible mechanisms for DPT in solution are explored: in the first one, water molecules only remain passive elements, whereas in the second one they are directly included in the reaction path. For the noncatalyzed mechanism, the stable structures constitute the canonical form of the base pair and the first proton transfer product. Nevertheless, by involving the two water molecules in the reaction, we found three stable species: canonical base pair, first proton transfer product, and double proton transfer product. Although the thermodynamic analysis confirms that AT does not contribute to spontaneous mutation through proton transfer catalyzed by surrounding water, our results suggest that microhydration may play a crucial role for DPT reaction in others DNA or RNA basis pair.

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“…Enzyme catalysis of horse liver alcohol dehydrogenase may be understood by a model of vibrationally enhanced proton transfer tunneling [10]. Furthermore, the double proton transfer reaction in DNA base pairs has been studied in detail and even been hypothesized as a possible source of spontaneous mutation [11][12][13].…”

Section: Quantum Tunneling Versus Classical Over Barrier Reactionsmentioning

confidence: 99%

Coherent Proton Tunneling in Hydrogen Bonds of Isolated Molecules: Carboxylic Dimers

Havenith¹

2006

Hydrogen‐Transfer Reactions

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IntroductionDue to the exceptional importance of hydrogen bonds in biology and chemistry the detailed investigation of their structure and dynamics has attracted the attention of several experimental and theoretical groups. Laser spectroscopic measurements and quantum mechanical calculations have led, in recent years, to remarkable progress towards the detailed understanding of important prototype systems such as (NH 3 ) 2 [1], (H 2 O) 2 [2], and DNA base pairs [3].Double hydrogen bonded systems play a crucial role in that they serve as model systems for the understanding of DNA base pairs. Proton transfer is of fundamental interest for biology as well as being a fundamental reaction in chemistry [4,5]. Moreover, multiple-proton transfer in hydrogen bonded systems is one of the most fundamental processes in biology and chemistry. It governs oxidationreduction reactions in many chemical and biological reactions [6]. In proton pumping mechanisms of trans membrane proteins protons are transported across the membrane by subsequent proton transfer. These reactions may incorporate strong quantum effects due to the low mass of the proton. The observation of pronounced isotopic effects is taken as an indication of a strong tunneling contribution. In contrast, the classical transmission probability is zero as long as the energy of the particle is lower than the barrier height (V ‡ ) and is equal to 1 if the energy (E) exceeds this. For an ensemble at temperature T this leads to the well known Arrhenius equation for the reaction rate which is proportional to exp (-(E -V ‡ )/ kT). The transmission will, therefore, depend solely on the barrier height and not on the width or on the exact shape of the transition barrier. Isotopic substitution will shift the zero point energies relative to the transition barrier and will, therefore, lead to a change in the reaction constant.Quantum mechanical tunneling is a result of the wavelike nature of particles which allows transmission through a reaction barrier. The quantum mechanical transmission probability for energies below V ‡ is governed by tunneling and reflection at the barrier. The transmission is larger than zero even well below the barrier and will depend crucially on the barrier width. In Hydrogen-Transfer Reactions. Edited by

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Molecular Dynamics Simulation of Double Proton Transfer: Adenine–Thymine Base Pair

Cited by 13 publications

References 28 publications

Theoretical thermodynamic study of the adenine-thymine tautomeric equilibrium: Electronic structure calculations and steered molecular dynamic simulations

Theoretical thermodynamic study of the adenine-thymine tautomeric equilibrium: Electronic structure calculations and steered molecular dynamic simulations

Effects of Hydration on the Proton Transfer Mechanism in the Adenine−Thymine Base Pair

Coherent Proton Tunneling in Hydrogen Bonds of Isolated Molecules: Carboxylic Dimers

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