CAREER: Physics of Virus Structure: Energetics and Dynamics

技术综述：这是一个支持凝聚态物理和生物学交界处的理论研究和教育的职业奖项。这项拟议研究的目的是建立一种针对病毒结构的统计机械调查，重点放在正确的(粗粒度)描述水平上，以捕捉基本物理，同时包括足够的生化细节，以开发可验证的模型来阐明病毒组装。特别是，将调查以下主要问题：(I)决定空壳的大小和形状的相关热力学控制参数是什么？(2)封闭的基因组对衣壳的大小和形状有什么影响，特别是对于共同组装的情况(基因组触发形成过程)？以及(Iii)所有这些因素对自组装动力学的影响是什么？空衣壳组装中的重要问题是蛋白质形状、疏水性和它们之间的屏蔽库仑相互作用之间的关系，以及二十面体、圆柱体和圆锥体组装的几何形状。这项研究将集中在病毒自组装的统计机制上，包括平衡和非平衡。由于衣壳组装类似于热力学相变，动力学将使用成核理论。此外，为了阐明封装链在确定病毒最佳大小方面所起的最简单的物理作用，聚电解质吸附的自洽场理论将扩展到受限几何图形。有趣的是，基因组长度和基因组/衣壳吸引相互作用的强度如何影响病毒颗粒的自由能。考虑到物理的复杂性，分析理论将通过标度方法、数值研究和计算机模拟来扩充。特别是，PI将执行一系列蒙特卡洛和布朗动力学计算机模拟，以探索病毒自组装的平衡和动力学方面。我们的模拟涉及一个模型衣壳蛋白系统，用于研究壳的大小和衣壳之间的对称性的选择。该奖项还有助于本科生、研究生和研究生的教育，特别是对下一代凝聚态物质和生物物理学家的培训。为河滨县和圣贝纳迪诺县的K-12级教师开展的外展计划，以及为妇女举办的讲习班，旨在提高代表人数不足的群体对科学的参与。非技术总结：这是一个支持凝聚态物理和生物学交界处的理论研究和教育的职业奖项。复制病毒颗粒的一个基本步骤是从其组成蛋白和封闭的基因组中自组装其刚性外壳(衣壳)。病毒的物理学非常丰富。它包括了解大分子(聚合物)在有限体积中的行为，以及基因组和衣壳的合作生长。虽然病毒的体外和体内组装被认为是生物学中自组装的范例，但支撑病毒结构的物理原理才刚刚开始被理解。PI将利用统计物理学的工具进行理论研究，以解决旨在提高我们对病毒结构和组装的理解的重要问题。由于衣壳在病毒的基因组复制和细胞间移动中起着至关重要的作用，了解病毒组装可能对开发新的抗病毒疗法和系统治疗病毒感染至关重要。这项研究还与材料科学的新兴领域相联系--合成用于包裹非遗传物质的病毒纳米容器和设计新型仿生材料。此外，由于病毒感染各种宿主(细菌、植物和动物)的程度不同(从普通感冒到艾滋病)，各级学生对了解病毒生命周期的机制产生了浓厚的兴趣。该奖项还有助于本科生、研究生和研究生的教育，特别是对下一代凝聚态物质和生物物理学家的培养。为河滨县和圣贝纳迪诺县的K-12级教师开展的外展计划，以及为妇女举办的讲习班，旨在提高代表人数不足的群体对科学的参与。

TECHNICAL SUMMARY:This is a CAREER award supports theoretical research and education at the interface of condensed matter physics and biology. The aim of the proposed research is to set up a statistical mechanical investigation of viral structure focusing on the right (coarse-grained) level of description to capture the essential physics, yet include sufficient biochemical details to develop verifiable models to elucidate viral assembly. In particular, the following major questions will be investigated: (i) What are the relevant thermodynamic control parameters that determine the size and shape of empty capsids? (ii) What is the effect of the enclosed genome on the size and shape of capsid, in particular for the case of co-assembly (where genome triggers the formation process)? And (iii) what are the effects of all these factors on the kinetics of self-assembly? Important issues in the assembly of empty capsids are the relation between protein shape, hydrophobic and screened-coulomb interactions between them, and the geometry of the icosahedral, cylindrical and conical assemblies. The research will focus on the statistical mechanics of viral self-assembly, both equilibrium and nonequilibrium. Since capsid assembly is akin to a thermodynamic phase transition, nucleation theory will be used for the kinetics. Furthermore, to elucidate the simplest physical role played by an encapsidated chain in determining the preferred size of a virus, the self-consistent field theory of polyelectrolyte adsorption will be extended to confined geometries. Of interest is how the free energy of viral particles is influenced by genome length and the strength of genome/capsid attractive interaction. In view of the complexity of the physics, the analytical theory is to be augmented by scaling methods, numerical investigations, and computer simulation. In particular, the PI will perform a series of Monte Carlo and Brownian dynamics computer simulations to explore the equilibrium and kinetic aspects of viral self-assembly. Our simulations involve a system of model capsid proteins for investigating the selection of shell size and symmetry among capsids.This award also contributes to the education of undergraduate, graduate and postgraduate students, and particularly to the training of the next generation of condensed matter and biological physicists. An outreach program for K-12 level teachers in the Riverside and San Bernardino counties, and workshops for women aim to improve participation of underrepresented groups in science. NON-TECHNICAL SUMMARY:This is a CAREER award supports theoretical research and education at the interface of condensed matter physics and biology. A fundamental step in the replication of a viral particle is the self-assembly of its rigid shell (capsid) from its constituent proteins and enclosed genome. The physics of viruses is exceptionally rich. It involves understanding the behavior of large molecules (polymers) in confined volumes and the co-operative growth of genomes and capsids. While the in vitro and in vivo assemblies of viruses are considered as the paradigm for self-assembly in biology, the physical principles that underlie virus structure are only beginning to be understood. The PI will carry out theoretical research using the tools of statistical physics to attack important problems aimed at improving our understanding of virus structure and assembly.Since capsids play a vital role in genome replication and intercellular movement of viruses, understanding viral assembly may be critical in the development of new anti-viral therapies and systematic treatment of viral infection. This research also connects with emerging areas of materials science - the synthesis of viral nano-containers for enclosing non-genetic material and designing novel biomimetic materials. Further, as viruses infect all kinds of hosts (bacteria, plants, and animals) with various degrees of severity (from the common cold to AIDS), there is keen interest among students at all levels to understand the mechanisms governing viral life cycle.This award also contributes to the education of undergraduate, graduate and postgraduate students, and particularly to the training of the next generation of condensed matter and biological physicists. An outreach program for K-12 level teachers in the Riverside and San Bernardino counties, and workshops for women aim to improve participation of underrepresented groups in science.