Monte Carlo simulation of radiolytic attack to 5'-d[T4G4] sequence in a unimolecular quadruplex

Abstract

Purpose: To extend to a quadruplex the stochastic model of radiolytic attack previously applied to a quasi-random duplex DNA. Materials and methods: The quadruplex structure is obtained from the PDB databank (first structure from 201D entry). The probabilities of OH radical attack at all sugar and base reaction sites are calculated using a stochastic model based on the Monte Carlo method. Results: Good agreement between the calculated and experimental frank strand break (FSB) probabilities is obtained using the relative efficiencies of conversion of the C4' and C5'-centred radicals into FSB determined for the quasi-random duplex (2.8:1 respectively). Efficiencies of base radicals-to-alkali-revealed breaks (ARB) conversion are determined by fitting the calculated probabilities of base attack to the previously reported experimental probabilities for ARB. The efficiency of conversion of thymine radical into an ARB is 3.4 +/- 0.7 times higher than for guanine radical. Conclusions: This paper supports the calculation method and allows evaluation of the relative efficiencies of thymine and guanine radicals-to-ARB conversion.