Models of topological barriers and molecular motors of bacterial DNA

Bacterial genomes are partitioned into kilobases long domains that are topologically independent from each other, meaning that change of DNA superhelicity in one domain does not propagate to neighbours. This is made possible by proteins like the LacI repressor, which behave like topological barriers and block the diffusion of torsion along the DNA. Other proteins, like DNA gyrases and RNA polymerases, called molecular motors, use the energy released by the hydrolysis of ATP to apply forces and/or torques to the DNA and modify its superhelicity. Here, we report on simulation work aimed at enlightening the interplay between DNA supercoiling, topological barriers, and molecular motors. To this end, we developed a coarse-grained Hamiltonian model of topological barriers and a model of molecular motors and investigated their properties through Brownian dynamics simulations. We discuss their influence on the contact map of a model nucleoid and the steady state values of twist and writhe in the DNA. These coarse-grained models, which are able to predict the dynamics of plectonemes depending on the position of topological barriers and molecular motors, should prove helpful to back up experimental efforts, like the development of Chromosome Conformation Capture techniques, and decipher the organisational mechanisms of bacterial chromosomes.

细菌基因组被划分为千碱基对长度的拓扑独立结构域，即单个结构域内的DNA超螺旋（DNA superhelicity）变化不会传播至相邻结构域。这一现象可通过LacI阻遏蛋白（LacI repressor）等拓扑屏障（topological barriers）类蛋白实现，这类蛋白可阻碍DNA沿链的扭转扩散。其他如DNA旋转酶（DNA gyrases）、RNA聚合酶（RNA polymerases）等被称为分子马达（molecular motors）的蛋白质，则利用ATP水解释放的能量，对DNA施加作用力和/或扭矩，进而改变其超螺旋状态。本研究针对DNA超螺旋、拓扑屏障与分子马达之间的相互作用展开模拟工作，以期阐明其内在关联。为此，我们构建了拓扑屏障的粗粒化哈密顿模型（coarse-grained Hamiltonian model）与分子马达模型，并通过布朗动力学模拟（Brownian dynamics simulations）对其特性展开研究。我们探讨了上述模型对模拟类核（nucleoid）接触图谱（contact map）以及DNA扭转（twist）与缠绕（writhe）稳态值的影响。这些粗粒化模型可依据拓扑屏障与分子马达的位置预测缠结超螺旋（plectonemes）的动态变化，有望为染色体构象捕获（Chromosome Conformation Capture, 3C）技术开发等实验研究提供支撑，并助力解析细菌染色体的组织机制。