Yu Kay Law - Predicting Thymine Dimerization Yields from Molecular Dynamics Simulations

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      Publication Details (including relevant citation   information):

      Law, Y. K., Azadi, J., Crespo-Hernandez, C. E., Olmon, E., and   Kohler, B. (2008) Predicting Thymine Dimerization Yields from   Molecular Dynamics Simulations, Biophys. J. 94, 3590-3600.

      Abstract:

      It was recently shown that thymine dimers in the all-thymine   oligonucleotide (dT)18 are fully formed in <1 ps after   ultraviolet excitation. The speed and low quantum yield of this   reaction suggest that only a small fraction of the conformers of   this structurally disordered oligonucleotide are in a position to   react at the instant of photon absorption. In this work, we   explore the hypothesis that conventional molecular dynamics   simulations can be used to predict the yield of cyclobutane   pyrimidine dimers in DNA. Conformations obtained from simulations   of thymidylyl-(3'-5')-thymidine in various cosolvents were   classified as dimerizable or nondimerizable depending on the   distance between the C5-C6 double bonds of the adjacent thymine   bases and the torsion angle between them. The quantum yield of   cyclobutane pyrimidine dimer formation was calculated as the   number of dimerizable conformations divided by the total number   of conformations. The experimental quantum yields measured in the   different solvents were satisfactorily reproduced using   physically reasonable values for the two parameters. The mean   dimerizable structure computed by averaging all of the   dimerizable cis-syn conformations is structurally similar to the   actual cis-syn dimer. Compared to the canonical B-form TT step,   the most important structural property of a dimerizable   conformation is its reduced helical twist angle of 22 degrees.

      Address (URL): http://www.cell.com/biophysj/abstract/S0006-3495%2808%2970435-1