Abstract
Proton transfer between the DNA bases can lead to non-standard, potentially mutagenic tautomeric forms [1, 2]. If the tautomers successfully pass through the replication machinery, they are thought to adopt a Watson-Crick-like shape and mismatch with the wrong base, thus evading proof-reading and potentially leading to replication error [3]. There is heated debate over the true biological impact of the tautomeric forms. Previously it was proposed that if the tautomeric lifetime is much shorter than the helicase cleavage time, no tautomeric population would successfully pass the enzyme [4]. Density functional theory (DFT) results suggest that the proton transfer energy landscape drastically changes during the first two Angstrom cleavage of the base. Molecular dynamics simulations indicate that cleavage time is much quicker than previously thought, with our models describing aqueous DNA. Our results indicate that a static picture of the proton transfer oversimplifies the biological event. [1] L. Slocombe, J. S. Al-Khalili, M. Sacchi, Phys. Chem. Chem. Phys., (2021), 23(7), pp.4141-4150. [2] O. Brovarets', D. Hovorun, J. Biomol. Struct. Dyn., (2018), 37(7), pp.1880-1907. [3] P. Löwdin, Rev. Mod. Phys., (1963), 35(3), pp.724. [4] O. Brovarets', D. Hovorun, J. Biomol. Struct. Dyn., (2014), 32(9), pp.1474-1499.