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

一些双链DNA病毒在高达50个大气压的压力下包装它们的基因组，并且比硬塑料更能承受外部变形。该项目侧重于从静态和动态角度研究病毒外壳内DNA和RNA压缩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，占主导地位的近距离DNA-DNA力，并被称为显着贡献的一些病毒的壳粒-壳粒缔合能量。国家的最先进的理论DNA-DNA静电相互作用和吸附到带相反电荷的表面将被实施来描述的半柔性DNA和柔性RNA链内的衣壳的压缩。将分析来自蛋白质和毒蛇数据库的病毒衣壳蛋白的详细分子结构，以合理化衣壳间的相互作用及其对衣壳的壳形状和弹性性质的影响。该项目的动力学部分的重点是解开拥挤的分子环境的细胞质上的动力学的衣壳自组装过程的影响。在这里，约束条件下的广义扩散过程的创新理论将被实施。这一建议将导致更好地理解DNA/RNA包装在病毒内部的有限几何形状和驱动力的衣壳自组装的物理机制，通过将纳米尺度上的核酸和病毒衣壳蛋白质的精细结构细节与整个病毒的可测量的宏观性质相关联。

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.