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数千碱基对长度的拓扑独立结构域，单个结构域内的DNA超螺旋变化不会传递至相邻结构域。这一现象的实现依赖于LacI阻遏蛋白（LacI repressor）这类拓扑屏障蛋白，它们可阻断扭转力沿DNA分子的扩散。而DNA旋转酶（DNA gyrase）、RNA聚合酶（RNA polymerase）等被称为分子马达（molecular motors）的蛋白质，则通过ATP水解释放的能量，对DNA施加作用力和/或扭转力矩，以此改变其超螺旋状态。本研究开展模拟工作，旨在阐明DNA超螺旋、拓扑屏障与分子马达之间的相互作用机制。为此，我们构建了拓扑屏障的粗粒化哈密顿（Hamiltonian）模型与分子马达模型，并通过布朗动力学（Brownian dynamics）模拟对二者的特性展开了研究。我们探讨了上述模型对模拟类核（nucleoid）接触图谱的影响，以及DNA内扭转（twist）与缠绕（writhe）的稳态值。此类粗粒化模型可依据拓扑屏障与分子马达的位置，预测超螺旋环（plectonemes）的动态变化，有望为染色体构象捕获（Chromosome Conformation Capture）技术等实验研究提供支撑，并助力解析细菌染色体的组织机制。