Molecular dynamics simulations of a DNA strand containing two thymine dimers

COMP 233

Lauren L O'Neil and Olaf Wiest, Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556
Two adjacent thymines, after irradiation of DNA with light produce the cis-syn cyclobutane thymine dimer (CPD). Thymine dimers block cell replication and transcription, ultimately resulting in cell death. The repair of thymine dimers in DNA by excess electrons has been previously studied. Excess electrons were incorporated into the system via irradiation of a modified thymine base (Tx) and repair of the two CPDs in the strand were monitored. The ratio of repair of the distal dimer to the proximal dimer was 2.4:1. The structural and electronic origins of this surprising finding are not known. MD simulations are used to study the structure and dynamics of CPD-containing DNA duplexes. Specifically, AMBER force fields were used and 9 ns simulations were run for both the flipped-in and flipped-out forms. The distance of the dimers from the electron injection point (Tx), the position of each dimer, the overall structure of the DNA duplex will then be correlated with the experimental results for different sequences.