Molecular dynamics simulations of the effects of ring-saturated thymine lesions on DNA structure

✍ Scribed by Karol Miaskiewicz; John Miller; Rick Ornstein; Roman Osman

• Publisher: Wiley (John Wiley & Sons)
• Year: 1995
• Tongue: English
• Weight: 999 KB
• Volume: 35
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.360350112

✦ Synopsis

The effect ofthymine lesions produced by radiation or oxidative damage on DNA structure was studied by molecular dynamics simulations ofnative and damaged DNA. Thymine in position 7 of native dodecamer d(CGCGAA TTCGCG)2 was replaced by one ofthe four thymine lesions 5-hydroxy-5,6-dihydrothymine, 6-hydroxy-5,6-dihydrothymine (thymine photohydrate), 5,6dihydroxy-5,6-dihydro-thymine (thymine glycol), and 5,6-dihydrothymine. Simulations were performed with Assisted Model Building with Energy Refinement force field. Solvent was represented by a rectangular box of water with periodic boundary conditions applied. A constant temperature and constant volume protocol was used. The observed level of distortions of DNA structure depends on the specific nature ofthe lesion. The 5,6-dihydrothymine does not cause distinguishable perturbations to DNA. Other lesions produce a dramatic increase in the rise parameter between the lesion and the 5' adjacent adenine. These changes are accompanied by weakening of Watson-Crick hydrogen bonds in the A6-Tl9 base pair on the 5' side ofthe lesion. The lesioned bases also show negative values of inclination relative to the helical axis. No changes in the pattern ofbackbone torsional angles are observed with any of the lesions incorporated into DNA. The structural distortions in DNA correlate well with known biological eflects of5,6-dihydrothymine and thymine glycol on such processes as polymerase action or recognition by repair enzymes.