Modelling nucleic acid compaction inside viruses and self-assembly of viral capsids

一些双链DNA病毒在高达~50atm的压力下包装它们的基因组，比硬塑料更能承受外部变形。本项目从静态和动态的角度，重点研究病毒壳内DNA和RNA紧凑的理论方面，以及衣壳自组装的物理化学性质。在静态部分，重点是静电效应，它主导着近距离的DNA-DNA力，并已知对许多病毒的衣壳-衣壳结合能有显著贡献。最先进的DNA-DNA静电相互作用和聚电解质在相反带电表面的吸附理论将被用来描述衣壳内半柔性DNA和柔性RNA链的紧凑。将对蛋白质和毒蛇数据库中的病毒衣壳蛋白的详细分子结构进行分析，以使衣壳之间的相互作用及其对衣壳形状和弹性性质的影响合理化。该项目的动态部分集中于揭示细胞质拥挤的分子环境对衣壳自组装过程动力学的影响。在这里，我们将实施约束下广义扩散过程的创新理论。这一建议将通过将核酸和病毒衣壳蛋白在纳米尺度上的精细结构细节与整个病毒的可测量的宏观性质联系起来，从而更好地理解在病毒内部以受限几何形状包装DNA/RNA背后的物理机制，以及衣壳自组装的驱动力。

Some double-stranded DNA viruses pack their genomes under pressures of up to ~50 atm and sustain external deformations better than hard plastics. This project focuses on theoretical aspects of DNA and RNA compaction inside viral shells and on physical-chemical properties of capsid self-assembly, both from static and dynamical perspective. In the static part, the emphasis is on electrostatic effects that dominate the close-range DNA-DNA forces and are known to significantly contribute to capsomer-capsomer association energies for a number of viruses. State-of-the-art theories of DNA-DNA electrostatic interactions and polyelectrolyte adsorption onto oppositely charged surfaces will be implemented to describe the compaction of semiflexible DNA and flexible RNA chains inside the capsids. The detailed molecular structures of viral capsid proteins from the Protein and Viper Data Banks are going to be analyzed in order to rationalize the inter-capsomer interactions and their implications for the shell shape and elastic properties of the capsids. The dynamical part of the project is focused on unraveling the implications of crowded molecular environments of the cell cytoplasm on the kinetics of the capsid self-assembly process. Here, the innovative theories of generalized diffusional processes under confinement are going to be implemented. This proposal will lead to a better understanding of physical mechanisms behind DNA/RNA packing in confined geometries inside viruses and of driving forces for capsid self-assembly by relating the fine structural details of nucleic acids and viral capsomer proteins on the nano-scale to measurable macroscopic properties of entire viruses.