Sequence-specific cleavage of DNA under ultrasound is due to intramolecular dynamics

The physical reason for the observed pattern of sequence-specific ultrasonic DNA cleavage is still unclear. The aim of this work was to identify a possible relationship between the context-dependent dynamics of nucleotides in the B-DNA double helix and the sequence-specificity of DNA cleavage. We present the results of MD simulations of the Drew-Dickerson dodecamer d(CGCGAATTCGCG)2 (DDD) on 2 μs trajectories in six force fields: AMBER (parm99, bsc0, bsc1, OL15) and CHARMM (Ch27 and Ch36). We analyzed the conformational dynamics at each position of DDD using several metrics. As a result, the comparison of molecular modeling data with the statistics of the relative intensities of cleavage of double-stranded DNA allowed us to identify two types of intramolecular conformational states, the combination of which facilitates ultrasound cleavage of the dinucleotide. Namely, this is an abrupt S → N transition of the furanose ring at the 5'-end of the dinucleotide to a region with a phase angle of less than 60°, as well as an acute angle between the C3'O3' bond in the 5'-terminal nucleotide and the global axis of the double helix.