title: Computational study of thymine dimer radical anion splitting in the self-repair process of duplex DNA.
abstract: Formation of the thymine dimer is one of the most important types of photochemical damage in DNA, responsible for several biological pathologies. Though specifically designed proteins (photolyases) can efficiently repair this type of damage in living cells, an autocatalytic activity of the DNA itself was recently discovered, allowing for a self-repair mechanism. In this paper, we provide the first molecular dynamics study of the splitting of thymine dimer radical anions, using a quantum mechanical/molecular mechanics (QM/MM) approach based on density functional theory (DFT) to describe the quantum region. A set of seven statistically representative molecular dynamics trajectories is analyzed. Our calculations predict an asynchronously concerted process in which C5-C5' bond breaking is barrierless while C6-C6' bond breaking is characterized by a small free energy barrier. An upper bound of 2.5 kcal/mol for this barrier is estimated. Moreover, the molecular dynamics study and the low free energy barrier involved in C6-C6' bond breaking characterize the full process as being an ultrafast reaction.
authors.affiliation: Physikalisch Chemisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. masson@pci.uzh.ch
authors.forename: Fanny
authors.initials: F
authors.lastname: Masson
authors.forename: Teodoro
authors.initials: T
authors.lastname: Laino
authors.forename: Ivano
authors.initials: I
authors.lastname: Tavernelli
authors.forename: Ursula
authors.initials: U
authors.lastname: Rothlisberger
authors.forename: Jürg
authors.initials: J
authors.lastname: Hutter
mesh_terms: D000838:Anions / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D004260:DNA Repair; D019281:Dimerization; D005609:Free Radicals / Q000737:chemistry; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D011740:Pyrimidine Dimers / Q000138:chemical synthesis / Q000737:chemistry*; D011789:Quantum Theory; D013941:Thymine / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000838:Anions; D005609:Free Radicals; D011740:Pyrimidine Dimers; D004247:DNA; D013941:Thymine