BII stability and base step flexibility of N6-adenine methylated GATC motifs

• Molecular dynamics simulations were performed on N6-adenine methylated GATC motifs
• The GA step has the highest propensity for BII form when hemimethylated.
• The increased BII propensity correlates with increased stacking interactions.
• Flexibility of AT and TC steps is marginally affected by methylation.
• Possible implications for SeqA selectivity and binding are discussed.

The effect of N6-adenine methylation on the flexibility and shape of palindromic GATC sequences has been investigated by molecular dynamics simulations. Variations in DNA backbone geometry were observed, which were dependent on the degree of methylation and the identity of the bases. While the effect was small, more frequent BI to BII conversions were observed in the GA step of hemimethylated DNA. The increased BII population of the hemimethylated system positively correlated with increased stacking interactions between methylated adenine and guanine, while stacking interactions decreased at the TC step for the fully methylated strand. The flexibility of the AT and TC steps was marginally affected by methylation, in a fashion that was correlated with stacking interactions. The facilitated BI to BII conversion in hemimethylated strands might be of importance for SeqA selectivity and binding.

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