Department of Integrative Structural and Computational Biology , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California , United States.
Center for Integrative Proteomics Research , Rutgers State University , 174 Frelinghuysen Road , Piscataway , New Jersey , United States.
J Phys Chem B. 2018 May 31;122(21):5441-5447. doi: 10.1021/acs.jpcb.7b11770. Epub 2018 Jan 25.
Mesoscale molecular modeling is providing a new window into the inner workings of living cells. Modeling of genomes, however, remains a technical challenge, due to their large size and complexity. We describe a lattice method for rapid generation of bacterial nucleoid models that integrates experimental data from a variety of biophysical techniques and provides a starting point for simulation and hypothesis generation. The current method builds models of a circular bacterial genome with supercoiled plectonemes, packed within the small space of the bacterial cell. Lattice models are generated for Mycoplasma genitalium and Escherichia coli nucleoids, and used to simulate interaction data. The method is rapid enough to allow generation of multiple models when analyzing structure/function relationships, and we demonstrate use of the lattice models in creation of an all-atom representation of an entire cell.
介观分子建模为了解活细胞的内部运作提供了一个新窗口。然而,由于基因组的体积大和复杂性,对其进行建模仍然是一个技术挑战。我们描述了一种快速生成细菌拟核模型的格点方法,该方法整合了来自各种生物物理技术的实验数据,并为模拟和假设生成提供了起点。当前的方法构建了带有超螺旋扭结的圆形细菌基因组模型,这些模型被包装在细菌细胞的小空间内。我们为生殖道支原体和大肠杆菌拟核生成了格点模型,并将其用于模拟相互作用数据。该方法足够快速,可以在分析结构/功能关系时生成多个模型,我们展示了如何在创建整个细胞的全原子表示形式中使用格点模型。