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，即单个结构域内的DNA超螺旋状态变化不会传播至相邻结构域。这类结构域的划分可借助LacI阻遏蛋白等拓扑屏障类蛋白实现，此类蛋白可充当拓扑屏障，阻断扭转力沿DNA链的扩散。另一类被称为分子马达的蛋白，如DNA旋转酶与RNA聚合酶，可利用ATP水解释放的能量，对DNA施加作用力与/或扭转力矩，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开展模拟工作，现将相关研究成果予以报道。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，并通过布朗动力学模拟对两类模型的特性展开研究。我们探讨了上述模型对模拟类核接触图谱的影响，以及DNA扭转（twist）与缠绕（writhe）的稳态数值特征。此类粗粒化模型可依据拓扑屏障与分子马达的位置，预测捻环（plectoneme）的动态变化，有望为染色体构象捕获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。