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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of chemical theory and computation 2019-12, Vol.15 (12), p.6984-6991
Main Authors: Soler-Polo, Diego, Mendieta-Moreno, Jesús I, Trabada, Daniel G, Mendieta, Jesús, Ortega, José
Format: Article
Language:English
Subjects:
Base Pairing
Cytosine - chemistry
Deoxyribonucleic acid
DNA
DNA, B-Form - chemistry
Free energy
Genetic code
Guanine - chemistry
Mathematical analysis
Mutation
Protons
Quantum mechanics
Quantum Theory
Tautomers
Vapor phases
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1549-9618
1549-9626
DOI:10.1021/acs.jctc.9b00757