Proton/Hydrogen Transfer Mechanisms in the Guanine鈥揅ytosine Base Pair: Photostability and Tautomerism

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• 作者：Vicenta Sauri ; Jo茫o P. Gobbo ; Juan J. Serrano-P茅rez ; Marcus Lundberg ; Pedro B. Coto ; Luis Serrano-Andr茅s ; Antonio C. Borin ; Roland Lindh ; Manuela Merch谩n ; Daniel Roca-Sanju谩n
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2013
• 出版时间：January 8, 2013
• 年：2013
• 卷：9
• 期：1
• 页码：481-496
• 全文大小：942K
• 年卷期：v.9,no.1(January 8, 2013)
• ISSN：1549-9626

文摘

Proton/hydrogen-transfer processes have been broadly studied in the past 50 years to explain the photostability and the spontaneous tautomerism in the DNA base pairs. In the present study, the CASSCF/CASPT2 methodology is used to map the two-dimensional potential energy surfaces along the stretched NH reaction coordinates of the guanine鈥揷ytosine (GC) base pair. Concerted and stepwise pathways are explored initially in vacuo, and three mechanisms are studied: the stepwise double proton transfer, the stepwise double hydrogen transfer, and the concerted double proton transfer. The results are consistent with previous findings related to the photostability of the GC base pair, and a new contribution to tautomerism is provided. The C-based imino-oxo and imino-enol GC tautomers, which can be generated during the UV irradiation of the Watson鈥揅rick base pair, have analogous radiationless energy-decay channels to those of the canonical base pair. In addition, the C-based imino-enol GC tautomer is thermally less stable. A study of the GC base pair is carried out subsequently taking into account the DNA surroundings in the biological environment. The most important stationary points are computed using the quantum mechanics/molecular mechanics (QM/MM) approach, suggesting a similar scenario for the proton/hydrogen-transfer phenomena in vacuo and in DNA. Finally, the static model is complemented by ab initio dynamic simulations, which show that vibrations at the hydrogen bonds can indeed originate hydrogen-transfer processes in the GC base pair. The relevance of the present findings for the rationalization of the preservation of the genetic code and mutagenesis is discussed.