Topological constraints, such as those associated with DNA supercoiling, play an integral role in genomic regulation and organization in living systems. However, physical understanding of the principles that underlie DNA organization at biologically relevant length scales remains a formidable challenge. We develop a coarse-grained simulation approach for predicting equilibrium conformations of supercoiled DNA. Our methodology enables the study of supercoiled DNA molecules at greater length scales and supercoiling densities than previously explored by simulation. With this approach, we study the conformational transitions that arise due to supercoiling across the full range of supercoiling densities that are commonly explored by living systems. Simulations of ring DNA molecules with lengths at the scale of topological domains in the Escherichia coli chromosome (?10 kilobases) reveal large-scale conformational transitions elicited by supercoiling. The conformational transitions result in three supercoiling conformational regimes that are governed by a competition among chiral coils, extended plectonemes, and branched hyper-supercoils. These results capture the nonmonotonic relationship of size versus degree of supercoiling observed in experimental sedimentation studies of supercoiled DNA, and our results provide a physical explanation of the conformational transitions underlying this behavior. The length scales and supercoiling regimes investigated here coincide with those relevant to transcription-coupled remodeling of supercoiled topological domains, and we discuss possible implications of these findings in terms of the interplay between transcription and topology in bacterial chromosome organization.
Algorithms Computer Simulation