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Results are presented from 500 ps molecular dynamics simulations on the native dodecamer d(CGCGAATTCGCG)2 and the lesioned dodecamer containing a cis,syn-thymine cyclobutane dimer at the TT step. The computations, performed with AMBER4.1, included explicitly represented solvent with periodic boundary conditions applied within the constant temperature and pressure algorithm. Electrostatic interactions were calculated with the particle-mesh Ewald method. Distortions to DNA structure produced by the lesion were found to be localized at the dimer site and include mainly a substantial kink in the helical axis, rolled and tilted base pairs, and weakened hydrogen bonding at the 5‘ base pair of the lesion. A slight change in orientation around the glycosyl bond for the 5‘ thymine of the lesion and highly stiffened deoxyribose rings for both thymine bases were also observed. The global curvature of DNA is increased by about 10° by dimer incorporation. Calculations of H(1‘)-H(6)(pyrimidine) and H(1‘)-H(8)(purine) interproton distances from the performed simulations agree very well with the pattern of NMR NOE signals reported in various dimer containing oligonucleotides, where an interruption of NOE connectivities is found on the 5‘ side of the lesion. Comparison of the pattern of distortions observed at the dimer site with the crystal structure of a complex between dimer-containing DNA and repair enzyme endonuclease V (Cell 1995, 83, 773−782) leads to the hypothesis that dimer recognition may involve a whole pattern of small distortion at the lesion site rather than one particular structural/dynamical feature associated with the lesion.

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