Molecular Dynamics Study of Supercoiled DNA Minicircles Tightly Bent and Supercoiled DNA in Atomistic Resolution

Towards the complete understanding of the DNA response to superhelical stress, sequence dependence structural disruptions on the ~100 base pairs supercoiled DNA minicircles were examined through a series of atomistic MD simulations. The results showed the effects from some subtle structural characteristics of DNA on defect formation, including flexibility at base pair step level and anisotropy, whose dynamic information are available only from atomistic MD simulations. For longer supercoiled DNA minicircles (240-340 bp), the molecules adapt into their writhed conformations. Writhe can be calculated by a Gauss’ integral performed along the DNA central axis path. A new mathematical definition for the DNA central axis path was developed for the more exact writhe calculation. Finally, atomistic representation of supercoiled 336 base pairs minicircles was provided by fitting the DNA structure obtained by explicitly solvated MD simulations into the density maps from electron cryo-tomography. Structural data were analysed and provided a decent explanation for the mechanism of the sequence specific binding of the enzyme topoisomerase 1B onto the negatively supercoiled DNA.