Replication of circular DNA proceeds through a stage of multiply interlinked catenanes that have to be rapidly spatially separated. In addition, knotting of circular DNA has also to be avoided. In bacteria, topology simplification requires participation of two type II topoisomerases: gyrase and topo IV. Several simulation approaches were applied to explain the very efficient topology simplification in that system. Mainly two strategies were explored: in the first one, the system follows its free energy gradient influenced by supercoiling, and in the second one, specific geometrical rules are defined for the selection of strand passages (hooking, chirality). The Monte-Carlo methods usually used to estimate the efficiency of these strategies do not allow to follow DNA topology simplification dynamically, to evaluate its speed, for example. To overcome this limitation, we simulated DNA unknotting and decatenation by Brownian dynamics, which allows for a natural integration of the strategies mentioned above. By following the topological state of the simulated DNA chains (see figure), we show that the combination of supercoiling and local geometrical selection rules provides an important drive for unknotting and decatenation, especially at low topological complexity.View Large Image | View Hi-Res Image | Download PowerPoint Slide