Genome MD: Molecular Dynamics Simulation of Genome Architecture
Gene expression in eukaryotic cells is regulated through the interaction of the long separated sites of DNA. Such interaction should be largely affected by the three dimensional organization of the genome in nucleus. We simulate the fluctuating dynamics of the genome architecture by using the ideas and methods to study protein dynamics: By using the average structure obtained from the ensemble of many cells, the fluctuation of chromosomes is simulated by using the structure-based Go-like model.
N. Tokuda, T. P. Terada, and M. Sasai, "Dynamical modeling of 3D genome organization in interphase budding yeast", Biophys. J. 102: 296-304 (2012)
N. Tokuda, M. Sasai, and G. Chikenji, "Roles of DNA looping in enhancer-blocking activity", Biophys. J. 100: 126-134 (2011).
In order to elucidate the physical mechanism of amoebic locomotion, a computational model is developed which highlights a group of inhibitory molecules for actin polymerization. Based on this model, we propose a hypothesis that inhibitory molecules are sent backward in the moving cell to accumulate at the rear of cell. The accumulated inhibitory molecules at the rear further promote cell locomotion to form a slow positive feedback loop of the whole-cell scale. The persistent straightforward migration is stabilized with this feedback mechanism, but the fluctuation in the distribution of inhibitory molecules and the cell shape deformation concurrently interrupt the persistent motion to turn the cell into a new direction. A sequence of switching behaviors between persistent motions and random turns gives rise to the superdiffusive migration in the absence of the external guidance signal. In the complex environment with obstacles, this combined process of persistent motions and random turns drives the simulated amoebae to solve the maze problem in a highly efficient way.
S. I. Nishimura, M. Ueda, and M. Sasai, "Non-Brownian dynamics and strategy of amoeboid cell locomotion", Phys. Rev. E 85: 041909_1-8 (2012).
S. I. Nishimura, M. Ueda, and M. Sasai, "Cortical factor feedback model of cellular locomotion and cytofission", PLoS Comp. Biol. 5: e1000310 (2009).