School of Mathematics, University of Minnesota, Twin Cities, Minneapolis, Minnesota.
Department of Mathematics, University of California Davis, Davis, California; Department of Molecular and Cellular Biology, University of California Davis, Davis, California.
Biophys J. 2021 Aug 17;120(16):3292-3302. doi: 10.1016/j.bpj.2021.07.006. Epub 2021 Jul 13.
Bacteriophages densely pack their long double-stranded DNA genome inside a protein capsid. The conformation of the viral genome inside the capsid is consistent with a hexagonal liquid crystalline structure. Experiments have confirmed that the details of the hexagonal packing depend on the electrochemistry of the capsid and its environment. In this work, we propose a biophysical model that quantifies the relationship between DNA configurations inside bacteriophage capsids and the types and concentrations of ions present in a biological system. We introduce an expression for the free energy that combines the electrostatic energy with contributions from bending of individual segments of DNA and Lennard-Jones-type interactions between these segments. The equilibrium points of this energy solve a partial differential equation that defines the distributions of DNA and the ions inside the capsid. We develop a computational approach that allows us to simulate much larger systems than what is possible using the existing molecular-level methods. In particular, we are able to estimate bending and repulsion between the DNA segments as well as the full electrochemistry of the solution, both inside and outside of the capsid. The numerical results show good agreement with existing experiments and with molecular dynamics simulations for small capsids.
噬菌体将其长长的双链 DNA 基因组紧密包装在蛋白质衣壳内。衣壳内病毒基因组的构象与六方液晶结构一致。实验已经证实,六方包装的细节取决于衣壳的电化学性质及其环境。在这项工作中,我们提出了一个生物物理模型,该模型量化了噬菌体衣壳内 DNA 构象与生物系统中存在的离子类型和浓度之间的关系。我们引入了一个自由能表达式,该表达式将静电能与 DNA 各段的弯曲以及这些段之间的 Lennard-Jones 型相互作用的贡献结合起来。这个能量的平衡点解决了一个偏微分方程,该方程定义了衣壳内 DNA 和离子的分布。我们开发了一种计算方法,使我们能够模拟比使用现有分子水平方法更大的系统。特别是,我们能够估计 DNA 片段之间的弯曲和排斥以及衣壳内外溶液的完整电化学。数值结果与现有实验和小衣壳的分子动力学模拟吻合良好。