Molecular dynamics simulation of a DNA duplex labeled with triarylmethyl spin radicals

Abstract

All-atom molecular dynamics simulation of aqueous solution of DNA duplex with triarylmethyl (TAM) spin labels attached to its ends through piperazine linkers has been carried out. The dynamics and structure of the resulting molecule on time scales up to 2μs has been studied. Two classes of specific conformations have been observed. In the first one, a duplex retains its structure, and the labels on the average are arranged above the end bases of the duplex. Another class is related to the appearance of fraying at the duplex ends, i.e. involves situations where bonds between the end bases are broken, and the end pair is open. In this case, the labels get additional opportunities for the movement. Furthermore, due to torsional rotations in the linker, large deviations from the equilibrium states are possible. It is discussed the detected fraying of duplex labeled with TAM is not the inevitable result of the impact of labels. Our additional simulation has shown that fraying also occurs in the duplex without labels. Thus, despite its size, the TAM spin label does not critically influence the structure of the duplex. The distribution of distance between the labels for conformations of duplex without fraying has been shown to be in good agreement with the experimental distribution measured by pulsed EPR for the same molecule immobilized on a substrate in an aqueous solution.