Physics of Viral Structure and Assembly

材料研究部和分子和细胞生物学部共同资助这一奖项。该奖项支持与生物学交界处的理论凝聚态物理学。PI试图开发一个全面的统计机械框架来描述病毒和病毒自组装的物理性质。新的实验提出了与病毒的结构稳定性、对称性和压力产生有关的基本问题。国际和平倡议旨在通过两个目标解决这些问题。第一个目标是为病毒结构和对称性提供物理基础，这是目前根据准等价原则和遗传简约性原则所证明的。自组装实验表明，这些概念必须基于自由能最小化。PI将采用多种方法的组合，目的是开发有意义的自由能。PI将利用统计力学模型进行病毒自组装，该模型已被证明既可以复制主要的二十面体衣壳系列，也可以复制特殊的非二十面体衣壳和圆柱形衣壳。将对该模型进行数值模拟，以确定完整的结构谱。结合这些结果和自组装系统的现代统计力学方法，PI将确定球状和棒状病毒组装的一般相图。这项工作将得到朗道理论的补充，以分析二十面体对称性和非二十面体结构之间的竞争。第二个目标是开发RNA封装的物理描述。噬菌体病毒的DNA封装由分子马达驱动，目前已经有了一种机械描述，但单链RNA病毒的自组装相当神秘：病毒RNA在组装过程中自发压缩，而不需要做任何外部功。我们将借用聚合物物理学中的经典分析方法来研究线性聚合物的自组装。为了解释RNA的二级和三级结构，我们将把Isambert和Siggia描述为一种热波动凝胶。利用连续介质弹性理论对胶囊化过程进行建模，得到自发组装的条件。Isamber-Siggia统计力学分析将被用来证明凝胶具有负的泊松比，这显然是连续介质描述所要求的。这项研究旨在将软凝聚态理论的现代方法扩展到病毒物理学中新出现的问题，如自组装、聚合物物理、熵弹性等领域。虽然人工蛋白质笼的合成是材料科学中一个快速发展的领域，但能够再现病毒衣壳显著特性的自组装壳的设计标准才刚刚开始被理解。正如自组装理论现在被用于纳米笼和量子点的常规自组装一样，对病毒自组装物理学的基本理解应该是设计合成蛋白质笼的有用指南。这项工作的一个更广泛的影响是，它有助于这一基本理解。它还为下一代凝聚态理论家提供研究生和研究生水平的教育经验。%材料研究部门和分子和细胞生物学部门共同资助该奖项。该奖项支持与生物学交界处的理论凝聚态物理学。PI试图开发一个全面的统计机械框架来描述病毒和病毒自组装的物理性质。病毒有助于将物理学应用于微生物学。这在一定程度上是因为与活的生物体相比，病毒结构极其严酷，而且它们不进行任何自主的新陈代谢过程。微机械操作方法和现代显微镜与分子生物学的结合现在正在产生新一代病毒的物理研究。这些实验提出了与结构稳定性、对称性和病毒压力产生有关的基本问题，PI将解决这些问题。这项研究旨在将软凝聚态理论的现代方法扩展到病毒物理学中新出现的问题，如自组装、聚合物物理、熵弹性等领域。虽然人工蛋白质笼的合成是材料科学中一个快速发展的领域，但能够再现病毒衣壳显著特性的自组装壳的设计标准才刚刚开始被理解。正如自组装理论现在被用于纳米笼和量子点的常规自组装一样，对病毒自组装物理学的基本理解应该是设计合成蛋白质笼的有用指南。这项工作的一个更广泛的影响是，它有助于这一基本理解。它还为下一代凝聚态理论家提供研究生和研究生水平的教育经验。*

The Division of Materials Research and the Division of Molecular and Cellular Biology jointly funds this award. This award supports theoretical condensed matter physics at the interface with biology. The PI seeks to develop a comprehensive statistical mechanical framework to describe the physical properties of viruses and of viral self-assembly. New experiments are raising basic questions relating to structural stability, symmetry, and pressure generation of viruses. The PI aims to address these questions with two objectives. The first objective is to provide a physical basis for viral structure and symmetry, which is currently justified in terms of the principles of quasi-equivalence and of genetic parsimony. Self-assembly experiments suggest that these concepts must be based on free energy minimization. The PI will employ a combination of methods with an aim to develop a meaningful free energy. The PI will utilize a statistical mechanical model for viral self-assembly that has been shown to reproduce both the main series of icosahedral capsids, exceptional non-icosahedral capsids and also cylindrical capsids. Numerical simulations of this model will be carried out to determine the full structure spectrum. Using these results together with modern statistical mechanical methods of self-assembling systems the PI will determine a general phase diagram for the assembly of both sphere-like and rod-like viruses. The work will be complemented by the use of Landau Theory to analyze the competition between icosahedral symmetry and non-icosahedral structures. The second objective is to develop a physical description of RNA encapsidation. A mechanical description of DNA encapsidation of phage viruses, which is powered by a molecular motor, is already available but the self-assembly of single-stranded RNA viruses is quite mysterious: viral RNA is spontaneously compressed during assembly without any external work being done. Self-assembly of linear polymers will be examined by classical analytical methods borrowed from polymer physics. In order to account for the secondary and tertiary RNA structure, we will apply the Isambert and Siggia description of RNA as a thermally fluctuating gel. Continuum elasticity theory will be used to model the encapsidation process and obtain the conditions for spontaneous assembly. The Isamber-Siggia statistical mechanical analysis will be used to demonstrate that the gel has negative Poisson Ratio, as apparently required by the continuum description. The research aims to extend modern methods of soft condensed matter theory, in areas such as self-assembly, polymer physics, entropic elasticity to emerging problems in the physics of viruses. While the synthesis of artificial protein cages is a rapidly developing area of materials science, the design criteria for self-assembled shells that can reproduce the remarkable properties of viral capsids are only beginning to be understood. Just as the theory of self-assembly now is used on a routine basis for the self-assembly of nanocages and quantum dots, a basic understanding of the physics of viral self-assembly should be a useful guide for the design of synthetic protein cages. A broader impact of this work is that it contributes to this basic understanding. It also provides graduate and postgraduate level educational experiences for the next generation of condensed matter theorists.%%%The Division of Materials Research and the Division of Molecular and Cellular Biology jointly funds this award. This award supports theoretical condensed matter physics at the interface with biology. The PI seeks to develop a comprehensive statistical mechanical framework to describe the physical properties of viruses and of viral self-assembly. Viruses lend themselves to the application of physics to microbiology. This is in part because of the extreme austerity of viral structure as compared with living organisms and because they do not carry out any autonomous metabolic processes. The combination of micro-mechanical manipulation methods and modern microscopy with molecular biology is now producing a new generation of physical studies of viruses. These experiments are raising basic questions relating to structural stability, symmetry, and pressure generation of viruses that the PI will address. The research aims to extend modern methods of soft condensed matter theory, in areas such as self-assembly, polymer physics, entropic elasticity to emerging problems in the physics of viruses. While the synthesis of artificial protein cages is a rapidly developing area of materials science, the design criteria for self-assembled shells that can reproduce the remarkable properties of viral capsids are only beginning to be understood. Just as the theory of self-assembly now is used on a routine basis for the self-assembly of nanocages and quantum dots, a basic understanding of the physics of viral self-assembly should be a useful guide for the design of synthetic protein cages. A broader impact of this work is that it contributes to this basic understanding. It also provides graduate and postgraduate level educational experiences for the next generation of condensed matter theorists.***