Photolyases are proteins capable of harvesting the sunlight to repair DNA damages caused by UV sunlight. In spite of great potential for use of photolyases in future sunscreen techniques for skin cancer prevention, the detailed mechanism of their operation still has not been established. In this work we focus on the first step in the repair process of the cyclobutane pyrimidine dimer (CPD) lesion (see Fig.), which is an electron transfer (ET) from a cofactor to CPD. Transient spectroscopy experiments measured the rate of this ET reaction [2], but this method lacks microscopic details so that conformations and active modes of the cofactor during the process remain unknown [2,3]. Based on previous theoretical studies of electronic structures and conformations of the active site of the protein [4], we build regularized diabatic models [5] using different set of active coordinates, and estimate ET rates for each model by the non-equilibrium Fermi's golden rule method [6]. Comparing our rate estimates to the experimental result allows us to differentiate between important modes of the cofactor and gives insights on its conformations inside the protein active site. [1] Berardesca, E., Bertona, M., Altabas, K., Altabas, V., and Emanuele, E. (2012) Mol. Med. Rep. 5 (2), 570. [2] Kao, Y.-T., Saxena, C., Wang, L., Sancar, A., and Zhong, D. (2005) Proc. Natl. Acad. Sci. USA. 102 (45), 16128. [3] Zheng, X., Garcia, J., and Stuchebrukhov, A. A., J. Phys. Chem.B 112, 8724 (2008). [4] Domratcheva, T. (2011) J. Am. Chem. Soc. 133 (45), 18172, and personal communication (2011). [5] H. Köppel and B. Schubert, Mol. Phys. 104, 1069 (2006). [6] A. F. Izmaylov, D. Mendive-Tapia, M. J. Bearpark, M. A. Robb, J. C. Tully, and M. J. Frisch, J. Chem. Phys. 135, 234106 (2011).

Theoretical study of the electron transfer in DNA repair process of the cyclobutane pyrimidine dimer lesion

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.