Theoretical thermodynamic study of the adenine–thymine tautomeric equilibrium: Electronic structure calculations and steered molecular dynamic simulations |
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| Authors: | Santiago Tolosa Jorge Antonio Sansón Antonio Hidalgo |
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| Affiliation: | Departamento de Ingeniería Química y Química Física, Universidad de Extremadura, Badajoz, Spain |
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| Abstract: | 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/6‐311++G(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. |
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| Keywords: | adenine– thymine electronic structure calculation proton transfer in solution steered molecular dynamic simulations tautomeric equilibrium thermodynamic properties |
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