Proton Transfer in Guanine-Cytosine Base Pairs in B-DNA
A double proton transfer reaction in a guanine-cytosine (GC) base pair has been proposed as a possible mechanism for rare tautomer (G*C*) formation and thus a source of spontaneous mutations. We analyze this system with free energy calculations based on extensive Quantum Mechanics/Molecular Mechanic...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad Francisco de Vitoria |
| Repositorio: | DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria |
| Idioma: | inglés |
| OAI Identifier: | oai:ddfv.ufv.es:10641/2237 |
| Acceso en línea: | http://hdl.handle.net/10641/2237 |
| Access Level: | acceso abierto |
| Sumario: | A double proton transfer reaction in a guanine-cytosine (GC) base pair has been proposed as a possible mechanism for rare tautomer (G*C*) formation and thus a source of spontaneous mutations. We analyze this system with free energy calculations based on extensive Quantum Mechanics/Molecular Mechanics simulations to properly consider the influence of the DNA biomolecular environment. We find that, although the G*C* rare tautomer is metastable in the gas phase, it is completely unstable in the conditions found in cells. Thus, our calculations show that a double proton reaction cannot be the source of spontaneous point mutations. We have also analyzed the intrabase H transfer reactions in guanine. Our results show that the DNA environment gives rise to a large free energy difference between the rare and canonical tautomers. These results show the key role of the DNA biological environment for the stability of the genetic code. |
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